bims-apauto Biomed News
on Apoptosis and autophagy
Issue of 2021‒02‒28
fourteen papers selected by
Su Hyun Lee
Seoul National University

  1. Nat Commun. 2021 Feb 26. 12(1): 1322
      The ubiquitin-proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34. We find that this ubiquitination enhances the binding of VPS34 to proteasomes for degradation, thereby suppressing autophagosome formation and maturation. Under ER and proteotoxic stresses, UBE3C recruitment to phagophores is compromised with a concomitant increase of its association with proteasomes. This switch attenuates the action of UBE3C on VPS34, thereby elevating autophagy activity to facilitate proteostasis, ER quality control and cell survival. Specifically in the liver, we show that TRABID-mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis. This study identifies a ubiquitination type on VPS34 and elucidates its cellular fate and physiological functions in proteostasis and liver metabolism.
  2. Eur Rev Med Pharmacol Sci. 2021 Feb;pii: 24875. [Epub ahead of print]25(3): 1641-1649
      Autophagy is a main metabolic process in which eukaryotic cells use lysosomes to eliminate abnormal proteins and damaged organelles to maintain cell homeostasis. Studies have revealed that neurodegenerative diseases, tumor, hepatic diseases, etc. are related to abnormal autophagy processes in recent years. Recent studies have shown that TFEB is a major transcription regulator of autophagy-lysosomal pathway (ALP) transcriptional regulation, which positively regulates the expression of autophagy and lysosomal biogenesis-related genes, thereby promoting autophagosome formation, autophagosome-lysosome fusion, and degradation of autophagy substrates. It has also been found that TFEB promotes clearance of intracellular substrates through lysosomal exocytosis. Therefore, the study of biological functions and related regulatory mechanisms of TFEB will provide important clues and theoretical basis for further explaining its physiological pathogenesis and the treatment of related diseases.
  3. Front Oncol. 2020 ;10 619727
      Cancer progression involves a variety of pro-tumorigenic biological processes including cell proliferation, migration, invasion, and survival. A cellular pathway implicated in these pro-tumorigenic processes is autophagy, a catabolic route used for recycling of cytoplasmic components to generate macromolecular building blocks and energy, under stress conditions, to remove damaged cellular constituents to adapt to changing nutrient conditions and to maintain cellular homeostasis. During autophagy, cells form a double-membrane sequestering a compartment termed the phagophore, which matures into an autophagosome. Following fusion with the lysosome, the cargo is degraded inside the autolysosomes and the resulting macromolecules released back into the cytosol for reuse. Cancer cells use this recycling system during cancer progression, however the key autophagy players involved in this disease is unclear. Accumulative evidences show that autophagy receptors, crucial players for selective autophagy, are overexpressed during cancer progression, yet the mechanisms whereby pro-tumorigenic biological processes are modulated by these receptors remains unknown. In this review, we summarized the most important findings related with the pro-tumorigenic role of autophagy receptors p62/SQSTM1, NBR1, NDP52, and OPTN in cancer progression. In addition, we showed the most relevant cargos degraded by these receptors that have been shown to function as critical regulators of pro-tumorigenic processes. Finally, we discussed the role of autophagy receptors in the context of the cellular pathways implicated in this disease, such as growth factors signaling, oxidative stress response and apoptosis. In summary, we highlight that autophagy receptors should be considered important players of cancer progression, which could offer a niche for the development of novel diagnosis and cancer treatment strategies.
    Keywords:  aggressiveness; autophagy; autophagy receptors; cancer progression; metastasis
  4. Autophagy. 2021 Feb 22.
      In humans, TDRD7 (tudor domain containing 7) mutations lead to a syndrome combining congenital cataracts (CCs) and non-obstructive azoospermia (NOA), characterized by abnormal lens development and spermiogenesis. However, the molecular mechanism underlying TDRD7's functions in eye and testicular development are still largely unknown. Here, we show that the depletion of this gene in mice and humans resulted in the accumulation of autophagosomes and the disruption of macroautophagic/autophagic flux. The disrupted autophagic flux in tdrd7-deficient mouse embryonic fibroblasts (MEFs) was caused by a failure of autophagosome fusion with lysosomes. Furthermore, transcriptome analysis and biochemical assays showed that TDRD7 might directly bind to Tbc1d20 mRNAs and downregulate its expression, which is a key regulator of autophagosome maturation, resulting in the disruption of autophagosome maturation. In addition, we provide evidence to show that TDRD7-mediated autophagosome maturation maintains lens transparency by facilitating the removal of damaged proteins and organelles from lens fiber cells and the biogenesis of acrosome. Altogether, our results showed that TDRD7 plays an essential role in the maturation of autophagosomes and that tdrd7 deletion results in eye defects and testicular abnormalities in mice, implicating disrupted autophagy might be the mechanism that contributes to lens development and spermiogenesis defects in human.
    Keywords:  TBC1D20; TDRD7; acrosome biogenesis; autophagy; lens development; spermiogenesis
  5. Autophagy. 2021 Feb 25. 1-3
      Phase-separated droplets with liquid-like properties can be degraded by macroautophagy/autophagy, but the mechanism underlying this degradation is poorly understood. We have recently derived a physical model to investigate the interaction between autophagic membranes and such droplets, uncovering that intrinsic wetting interactions underlie droplet-membrane contacts. We found that the competition between droplet surface tension and the increasing tendency of growing membrane sheets to bend determines whether a droplet is completely engulfed or isolated in a piecemeal fashion, a process we term fluidophagy. Intriguingly, we found that another critical parameter of droplet-membrane interactions, the spontaneous curvature of the membrane, determines whether the droplet is degraded by autophagy or - counterintuitively - serves as a platform from which autophagic membranes expand into the cytosol. We also discovered that the interaction of membrane-associated LC3 with the LC3-interacting region (LIR) found in the autophagic cargo receptor protein SQSTM1/p62 and many other autophagy-related proteins influences the preferred bending directionality of forming autophagosomes in living cells. Our study provides a physical account of how droplet-membrane wetting underpins the structure and fate of forming autophagosomes.
    Keywords:  Autophagy; condensate; droplet; isolation membrane; membrane; p62; phase separation; piecemeal autophagy; wetting
  6. Autophagy. 2021 Feb 23. 1-15
      Alzheimer disease (AD) is the most prevalent neurodegenerative disorder leading to dementia in the elderly. Unfortunately, no cure for AD is available to date. Increasing evidence has proved the roles of misfolded protein aggregation due to impairment of the macroautophagy/autophagy-lysosomal pathway (ALP) in the pathogenesis of AD, and thus making TFEB (transcription factor EB), which orchestrates ALP, as a promising target for treating AD. As a complementary therapy, acupuncture or electroacupuncture (EA) has been commonly used for treating human diseases. Although the beneficial effects of acupuncture for AD have been primarily studied both pre-clinically and clinically, the real efficacy of acupuncture on AD remains inconclusive and the underlying mechanisms are largely unexplored. In this study, we demonstrated the cognitive-enhancing effect of three-needle EA (TNEA) in an animal model of AD with beta-amyloid (Aβ) pathology (5xFAD). TNEA reduced APP (amyloid beta (A4) precursor protein), C-terminal fragments (CTFs) of APP and Aβ load, and inhibited glial cell activation in the prefrontal cortex and hippocampus of 5xFAD. Mechanistically, TNEA activated TFEB via inhibiting the AKT-MAPK1-MTORC1 pathway, thus promoting ALP in the brains. Therefore, TNEA represents a promising acupuncture therapy for AD, via a novel mechanism involving TFEB activation.Abbreviations Aβ: β-amyloid; AD: Alzheimer disease; AIF1/IBA1: allograft inflammatory factor 1; AKT1: thymoma viral proto-oncogene 1; ALP: autophagy-lysosomal pathway; APP: amyloid beta (A4) precursor protein; BACE1: beta-site APP cleaving enzyme 1; CQ: chloroquine; CTFs: C-terminal fragments; CTSD: cathepsin D; EA: electroacupuncture; FC: fear conditioning; GFAP: glial fibrillary acidic protein; HI: hippocampus; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPT: microtubule-associated protein tau; MTORC1: mechanistic target of rapamycin kinase complex 1; MWM: Morris water maze; NFT: neurofibrillary tangles; PFC: prefrontal cortex; PSEN1: presenilin 1; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TNEA: three-needle electroacupuncture.
    Keywords:  Alzheimer disease; autophagy-lysosomal pathway; electroacupuncture; transcription factor EB
  7. Dev Cell. 2021 02 22. pii: S1534-5807(21)00113-1. [Epub ahead of print]56(4): 400-402
      Many pathogens are capable of disrupting autophagy within host cells. In this issue of Developmental Cell, Miao et al. discover that the SARS-CoV-2 protein ORF3a inhibits autophagosome-lysosome fusion by dysregulating the HOPS complex.
  8. Bioengineered. 2021 Dec;12(1): 697-707
      Growing evidences suggest that autophagy plays a momentous part in the tumorigenesis and development of hepatocellular carcinoma (HCC). However, there are not many researches to predict the prognosis of HCC using autophagy-related genes. Therefore, based on the clinical information and RNA-Seq data of The Cancer Genome Atlas data portal (TCGA), 13 autophagy‑related gene pairs were screened to build the autophagy‑related signature to predict the prognosis by least absolute shrinkage and selection operator (LASSO) regression analysis. Besides, the International Cancer Genome Consortium (ICGC) cohort was further applied to verify the autophagy‑related prognostic signature. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were also used to predict the relevant function of the autophagy-related gene pairs signature. As shown in the results, the autophagy-related gene pairs were mainly involved in process utilizing autophagic mechanism, autophagy, macroautophagy and cellular response to oxidative stress. The immune cell levels in the high-risk and low-risk group were explored, which showed that the three immune cells were obviously increased in the high-risk group, while the five immune cells were obviously increased in the low-risk group. In conclusion, an autophagy‑related prognostic signature was established to predict the prognosis of HCC patients with great accuracy and we found that autophagy‑related prognostic signature was related to infiltrating immune cells.
    Keywords:  Autophagy-related gene pairs; hepatocellular carcinoma; immune; prognosis
  9. Curr Biol. 2021 Feb 17. pii: S0960-9822(21)00146-9. [Epub ahead of print]
      Mutations in WDR45 and WDR45B cause the human neurological diseases β-propeller protein-associated neurodegeneration (BPAN) and intellectual disability (ID), respectively. WDR45 and WDR45B, along with WIPI1 and WIPI2, belong to a WD40 repeat-containing phosphatidylinositol-3-phosphate (PI(3)P)-binding protein family. Their yeast homolog Atg18 forms a complex with Atg2 and is required for autophagosome formation in part by tethering isolation membranes (IMs) (autophagosome precursor) to the endoplasmic reticulum (ER) to supply lipid for IM expansion in the autophagy pathway. The exact functions of WDR45/45B are unclear. We show here that WDR45/45B are specifically required for neural autophagy. In Wdr45/45b-depleted cells, the size of autophagosomes is decreased, and this is rescued by overexpression of ATG2A, providing in vivo evidence for the lipid transfer activity of ATG2-WIPI complexes. WDR45/45B are dispensable for the closure of autophagosomes but essential for the progression of autophagosomes into autolysosomes. WDR45/45B interact with the tether protein EPG5 and target it to late endosomes/lysosomes to promote autophagosome maturation. In the absence of Wdr45/45b, formation of the fusion machinery, consisting of SNARE proteins and EPG5, is dampened. BPAN- and ID-related mutations of WDR45/45B fail to rescue the autophagy defects in Wdr45/45b-deficient cells, possibly due to their impaired binding to EPG5. Promoting autophagosome maturation by inhibiting O-GlcNAcylation increases SNARE complex formation and facilitates the fusion of autophagosomes with late endosomes/lysosomes in Wdr45/45b double knockout (DKO) cells. Thus, our results uncover a novel function of WDR45/45B in autophagosome-lysosome fusion and provide molecular insights into the development of WDR45/WDR45B mutation-associated diseases.
    Keywords:  BPAN; ID; WDR45; WDR45B; autophagy
  10. Autophagy. 2021 Feb 25.
      The mechanisms orchestrating recycling of lysosomes through autophagic lysosome reformation (ALR) is incompletely understood. Previous data show that genetic depletion of BLOC1S1/GCN5L1/BORCS1 increases autolysosome (AL) accumulation. We postulated that this phenotype may manifest due to perturbed ALR. We explored this in control and bloc1s1 liver-specific knockout (LKO) mouse hepatocytes, showing that in response to nutrient-deprivation LKO's fail to initiate ALR due to blunted lysosomal tubulation. As kinesin motor proteins and the intracellular cytoskeleton are requirements for tubular formation from ALs, we explored the interaction of BLOC1S1 with motor proteins and cytoskeletal factors. BLOC1S1 interacts with the ARL8B-KIF5B (GTPase and kinesin motor protein) complex to recruit KIF5B to ALs. Furthermore, BLOC1S1 interacts with the actin nucleation promoting factor WHAMM, which is an essential structural protein in the initiation of lysosomal tubulation (LT). Interestingly, the genetic reintroduction of BLOC1S1 rescues LT in LKO hepatocytes, but not when KIF5B is concurrently depleted. Finally, given the central role of MTORC1 signaling in ALR initiation, it was interesting that MTORC1 activity was increased despite the absence of LT in LKO hepatocytes. Concurrently, inhibition of MTORC1 abolished BLOC1S1 reconstitution-mediated rescue of LT in LKO hepatocytes. Taken together these data demonstrate that the functional interaction of BLOC1S1 with the kinesin binding complex and the actin cytoskeleton are a requirement for LT which, in parallel with MTORC1 signaling, initiate lysosome recycling via ALR.
    Keywords:  Autophagic lysosome reformation; GCN5L1; MTORC1; autophagy; hepatocyte; lysosomal tubulation; lysosome
  11. Autophagy. 2021 Feb 25. 1-3
      Neurons are long-lived cells that communicate via release of neurotransmitter at specialized contacts termed synapses. The maintenance of neuronal health and the regulation of synaptic function requires the efficient removal of damaged or dispensable proteins and organelles from synapses. How macroautophagy/autophagy contributes to neuronal and synaptic protein turnover, and what its main physiological substrates are in healthy neurons is largely unknown. We have now shown that loss of neuronal autophagy facilitates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum and, thereby, axonal and synaptic calcium homeostasis.
    Keywords:  Autophagy; SV protein; calcium; endoplasmic reticulum; er-phagy; neurotransmission; reticulophagy; ryanodine receptor; synapse
  12. Carcinogenesis. 2021 Feb 24. pii: bgab016. [Epub ahead of print]
      The incidence of malignant melanoma, a neoplasm of melanocytic cells, is increasing rapidly. The lymph nodes are often the first site of metastasis and can herald systemic dissemination, which is almost uniformly fatal. RLIP, a multi-specific ATP-dependent transporter that is over-expressed in several types of cancers, plays a central role in cancer cell resistance to radiation and chemotherapy. RLIP appears to be necessary for cancer cell survival because both in-vitro cell culture and in-vivo animal tumor studies show that the depletion or inhibition of RLIP causes selective toxicity to malignant cells. RLIP depletion/inhibition triggers apoptosis in cancer cells by inducing the accumulation of endogenously formed glutathione-conjugates. In our in-vivo studies, we administered RLIP antibodies or antisense oligonucleotides to mice bearing subcutaneous xenografts of SKMEL2 and SKMEL5 melanoma cells and demonstrated that both treatments caused significant xenograft regression with no apparent toxic effects. Anti-RLIP antibodies and antisense, which respectively inhibit RLIP-mediated transport and deplete RLIP expression, showed similar tumor regressing activities, indicating that the inhibition of RLIP transport activity at the cell surface is sufficient to achieve anti-tumor activity. Furthermore, RLIP antisense treatment reduced levels of RLIP, pSTAT3, pJAK2, pSrc, Mcl-1, and Bcl2, as well as CDK4 and cyclin B1, and increased levels of Bax and pAMPK. These studies indicate that RLIP serves as a key effector in the survival of melanoma cells and is a valid target for cancer therapy. Overall, compounds that inhibit, deplete, or downregulate RLIP will function as wide-spectrum agents to treat melanoma, independent of common signaling pathway mutations.
    Keywords:  AMPK; JAK2/STAT3; Melanoma; RLIP; tumor xenografts
  13. Biosci Biotechnol Biochem. 2021 Feb 24. 85(3): 621-625
      Puerarin can protect chondrocytes, whereby ameliorating osteoarthritis. Puerarin also promotes autophagy. Autophagy maintains chondrocyte homeostasis. The role of autophagy in puerarin-protected chondrocytes is unknown. Puerarin promoted chondrocyte autophagy. Puerarin-protected chondrocytes were reversed by autophagy inhibitors and Beclin1 inhibitor. 3-MA or Beclin1 inhibitor in vivo reversed puerarin-ameliorated cartilage damage of osteoarthritis mice. Thus, puerarin can protect chondrocytes through Beclin1-dependent autophagy activation.
    Keywords:  Beclin1; Puerarin; autophagy; chondrocyte; osteoarthritis
  14. Autophagy. 2021 Feb 08. 1-382
    Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar PV, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gómez E, Alessandri C, Ali M, Alim Al-Bari MA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Álvarez ÉMC, Alves S, Alves da Costa C, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Antón Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araújo WL, Araya J, Arden C, Arévalo MA, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnauné-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R, Avagliano L, Ávalos Y, Aveic S, Aveleira CA, Avin-Wittenberg T, Aydin Y, Ayton S, Ayyadevara S, Azzopardi M, Baba M, Backer JM, Backues SK, Bae DH, Bae ON, Bae SH, Baehrecke EH, Baek A, Baek SH, Baek SH, Bagetta G, Bagniewska-Zadworna A, Bai H, Bai J, Bai X, Bai Y, Bairagi N, Baksi S, Balbi T, Baldari CT, Balduini W, Ballabio A, Ballester M, Balazadeh S, Balzan R, Bandopadhyay R, Banerjee S, Banerjee S, Bánréti Á, Bao Y, Baptista MS, Baracca A, Barbati C, Bargiela A, Barilà D, Barlow PG, Barmada SJ, Barreiro E, Barreto GE, Bartek J, Bartel B, Bartolome A, Barve GR, Basagoudanavar SH, Bassham DC, Bast RC, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR, Beers MF, Begun J, Behrends C, Behrens GMN, Bei R, Bejarano E, Bel S, Behl C, Belaid A, Belgareh-Touzé N, Bellarosa C, Belleudi F, Belló Pérez M, Bello-Morales R, Beltran JSO, Beltran S, Benbrook DM, Bendorius M, Benitez BA, Benito-Cuesta I, Bensalem J, Berchtold MW, Berezowska S, Bergamaschi D, Bergami M, Bergmann A, Berliocchi L, Berlioz-Torrent C, Bernard A, Berthoux L, Besirli CG, Besteiro S, Betin VM, Beyaert R, Bezbradica JS, Bhaskar K, Bhatia-Kissova I, Bhattacharya R, Bhattacharya S, Bhattacharyya S, Bhuiyan MS, Bhutia SK, Bi L, Bi X, Biden TJ, Bijian K, Billes VA, Binart N, Bincoletto C, Birgisdottir AB, Bjorkoy G, Blanco G, Blas-Garcia A, Blasiak J, Blomgran R, Blomgren K, Blum JS, Boada-Romero E, Boban M, Boesze-Battaglia K, Boeuf P, Boland B, Bomont P, Bonaldo P, Bonam SR, Bonfili L, Bonifacino JS, Boone BA, Bootman MD, Bordi M, Borner C, Bornhauser BC, Borthakur G, Bosch J, Bose S, Botana LM, Botas J, Boulanger CM, Boulton ME, Bourdenx M, Bourgeois B, Bourke NM, Bousquet G, Boya P, Bozhkov PV, Bozi LHM, Bozkurt TO, Brackney DE, Brandts CH, Braun RJ, Braus GH, Bravo-Sagua R, Bravo-San Pedro JM, Brest P, Bringer MA, Briones-Herrera A, Broaddus VC, Brodersen P, Brodsky JL, Brody SL, Bronson PG, Bronstein JM, Brown CN, Brown RE, Brum PC, Brumell JH, Brunetti-Pierri N, Bruno D, Bryson-Richardson RJ, Bucci C, Buchrieser C, Bueno M, Buitrago-Molina LE, Buraschi S, Buch S, Buchan JR, Buckingham EM, Budak H, Budini M, Bultynck G, Burada F, Burgoyne JR, Burón MI, Bustos V, Büttner S, Butturini E, Byrd A, Cabas I, Cabrera-Benitez S, Cadwell K, Cai J, Cai L, Cai Q, Cairó M, Calbet JA, Caldwell GA, Caldwell KA, Call JA, Calvani R, Calvo AC, Calvo-Rubio Barrera M, Camara NO, Camonis JH, Camougrand N, Campanella M, Campbell EM, Campbell-Valois FX, Campello S, Campesi I, Campos JC, Camuzard O, Cancino J, Candido de Almeida D, Canesi L, Caniggia I, Canonico B, Cantí C, Cao B, Caraglia M, Caramés B, Carchman EH, Cardenal-Muñoz E, Cardenas C, Cardenas L, Cardoso SM, Carew JS, Carle GF, Carleton G, Carloni S, Carmona-Gutierrez D, Carneiro LA, Carnevali O, Carosi JM, Carra S, Carrier A, Carrier L, Carroll B, Carter AB, Carvalho AN, Casanova M, Casas C, Casas J, Cassioli C, Castillo EF, Castillo K, Castillo-Lluva S, Castoldi F, Castori M, Castro AF, Castro-Caldas M, Castro-Hernandez J, Castro-Obregon S, Catz SD, Cavadas C, Cavaliere F, Cavallini G, Cavinato M, Cayuela ML, Cebollada Rica P, Cecarini V, Cecconi F, Cechowska-Pasko M, Cenci S, Ceperuelo-Mallafré V, Cerqueira JJ, Cerutti JM, Cervia D, Cetintas VB, Cetrullo S, Chae HJ, Chagin AS, Chai CY, Chakrabarti G, Chakrabarti O, Chakraborty T, Chakraborty T, Chami M, Chamilos G, Chan DW, Chan EYW, Chan ED, Chan HYE, Chan HH, Chan H, Chan MTV, Chan YS, Chandra PK, Chang CP, Chang C, Chang HC, Chang K, Chao J, Chapman T, Charlet-Berguerand N, Chatterjee S, Chaube SK, Chaudhary A, Chauhan S, Chaum E, Checler F, Cheetham ME, Chen CS, Chen GC, Chen JF, Chen LL, Chen L, Chen L, Chen M, Chen MK, Chen N, Chen Q, Chen RH, Chen S, Chen W, Chen W, Chen XM, Chen XW, Chen X, Chen Y, Chen YG, Chen Y, Chen Y, Chen YJ, Chen YQ, Chen ZS, Chen Z, Chen ZH, Chen ZJ, Chen Z, Cheng H, Cheng J, Cheng SY, Cheng W, Cheng X, Cheng XT, Cheng Y, Cheng Z, Chen Z, Cheong H, Cheong JK, Chernyak BV, Cherry S, Cheung CFR, Cheung CHA, Cheung KH, Chevet E, Chi RJ, Chiang AKS, Chiaradonna F, Chiarelli R, Chiariello M, Chica N, Chiocca S, Chiong M, Chiou SH, Chiramel AI, Chiurchiù V, Cho DH, Choe SK, Choi AMK, Choi ME, Choudhury KR, Chow NS, Chu CT, Chua JP, Chua JJE, Chung H, Chung KP, Chung S, Chung SH, Chung YL, Cianfanelli V, Ciechomska IA, Cifuentes M, Cinque L, Cirak S, Cirone M, Clague MJ, Clarke R, Clementi E, Coccia EM, Codogno P, Cohen E, Cohen MM, Colasanti T, Colasuonno F, Colbert RA, Colell A, Čolić M, Coll NS, Collins MO, Colombo MI, Colón-Ramos DA, Combaret L, Comincini S, Cominetti MR, Consiglio A, Conte A, Conti F, Contu VR, Cookson MR, Coombs KM, Coppens I, Corasaniti MT, Corkery DP, Cordes N, Cortese K, Costa MDC, Costantino S, Costelli P, Coto-Montes A, Crack PJ, Crespo JL, Criollo A, Crippa V, Cristofani R, Csizmadia T, Cuadrado A, Cui B, Cui J, Cui Y, Cui Y, Culetto E, Cumino AC, Cybulsky AV, Czaja MJ, Czuczwar SJ, D'Adamo S, D'Amelio M, D'Arcangelo D, D'Lugos AC, D'Orazi G, da Silva JA, Dafsari HS, Dagda RK, Dagdas Y, Daglia M, Dai X, Dai Y, Dai Y, Dal Col J, Dalhaimer P, Dalla Valle L, Dallenga T, Dalmasso G, Damme M, Dando I, Dantuma NP, Darling AL, Das H, Dasarathy S, Dasari SK, Dash S, Daumke O, Dauphinee AN, Davies JS, Dávila VA, Davis RJ, Davis T, Dayalan Naidu S, De Amicis F, De Bosscher K, De Felice F, De Franceschi L, De Leonibus C, de Mattos Barbosa MG, De Meyer GRY, De Milito A, De Nunzio C, De Palma C, De Santi M, De Virgilio C, De Zio D, Debnath J, DeBosch BJ, Decuypere JP, Deehan MA, Deflorian G, DeGregori J, Dehay B, Del Rio G, Delaney JR, Delbridge LMD, Delorme-Axford E, Delpino MV, Demarchi F, Dembitz V, Demers ND, Deng H, Deng Z, Dengjel J, Dent P, Denton D, DePamphilis ML, Der CJ, Deretic V, Descoteaux A, Devis L, Devkota S, Devuyst O, Dewson G, Dharmasivam M, Dhiman R, di Bernardo D, Di Cristina M, Di Domenico F, Di Fazio P, Di Fonzo A, Di Guardo G, Di Guglielmo GM, Di Leo L, Di Malta C, Di Nardo A, Di Rienzo M, Di Sano F, Diallinas G, Diao J, Diaz-Araya G, Díaz-Laviada I, Dickinson JM, Diederich M, Dieudé M, Dikic I, Ding S, Ding WX, Dini L, Dinić J, Dinic M, Dinkova-Kostova AT, Dionne MS, Distler JHW, Diwan A, Dixon IMC, Djavaheri-Mergny M, Dobrinski I, Dobrovinskaya O, Dobrowolski R, Dobson RCJ, Đokić J, Dokmeci Emre S, Donadelli M, Dong B, Dong X, Dong Z, Dorn Ii GW, Dotsch V, Dou H, Dou J, Dowaidar M, Dridi S, Drucker L, Du A, Du C, Du G, Du HN, Du LL, du Toit A, Duan SB, Duan X, Duarte SP, Dubrovska A, Dunlop EA, Dupont N, Durán RV, Dwarakanath BS, Dyshlovoy SA, Ebrahimi-Fakhari D, Eckhart L, Edelstein CL, Efferth T, Eftekharpour E, Eichinger L, Eid N, Eisenberg T, Eissa NT, Eissa S, Ejarque M, El Andaloussi A, El-Hage N, El-Naggar S, Eleuteri AM, El-Shafey ES, Elgendy M, Eliopoulos AG, Elizalde MM, Elks PM, Elsasser HP, Elsherbiny ES, Emerling BM, Emre NCT, Eng CH, Engedal N, Engelbrecht AM, Engelsen AST, Enserink JM, Escalante R, Esclatine A, Escobar-Henriques M, Eskelinen EL, Espert L, Eusebio MO, Fabrias G, Fabrizi C, Facchiano A, Facchiano F, Fadeel B, Fader C, Faesen AC, Fairlie WD, Falcó A, Falkenburger BH, Fan D, Fan J, Fan Y, Fang EF, Fang Y, Fang Y, Fanto M, Farfel-Becker T, Faure M, Fazeli G, Fedele AO, Feldman AM, Feng D, Feng J, Feng L, Feng Y, Feng Y, Feng W, Fenz Araujo T, Ferguson TA, Fernández ÁF, Fernandez-Checa JC, Fernández-Veledo S, Fernie AR, Ferrante AW, Ferraresi A, Ferrari MF, Ferreira JCB, Ferro-Novick S, Figueras A, Filadi R, Filigheddu N, Filippi-Chiela E, Filomeni G, Fimia GM, Fineschi V, Finetti F, Finkbeiner S, Fisher EA, Fisher PB, Flamigni F, Fliesler SJ, Flo TH, Florance I, Florey O, Florio T, Fodor E, Follo C, Fon EA, Forlino A, Fornai F, Fortini P, Fracassi A, Fraldi A, Franco B, Franco R, Franconi F, Frankel LB, Friedman SL, Fröhlich LF, Frühbeck G, Fuentes JM, Fujiki Y, Fujita N, Fujiwara Y, Fukuda M, Fulda S, Furic L, Furuya N, Fusco C, Gack MU, Gaffke L, Galadari S, Galasso A, Galindo MF, Gallolu Kankanamalage S, Galluzzi L, Galy V, Gammoh N, Gan B, Ganley IG, Gao F, Gao H, Gao M, Gao P, Gao SJ, Gao W, Gao X, Garcera A, Garcia MN, Garcia VE, García-Del Portillo F, Garcia-Escudero V, Garcia-Garcia A, Garcia-Macia M, García-Moreno D, Garcia-Ruiz C, García-Sanz P, Garg AD, Gargini R, Garofalo T, Garry RF, Gassen NC, Gatica D, Ge L, Ge W, Geiss-Friedlander R, Gelfi C, Genschik P, Gentle IE, Gerbino V, Gerhardt C, Germain K, Germain M, Gewirtz DA, Ghasemipour Afshar E, Ghavami S, Ghigo A, Ghosh M, Giamas G, Giampietri C, Giatromanolaki A, Gibson GE, Gibson SB, Ginet V, Giniger E, Giorgi C, Girao H, Girardin SE, Giridharan M, Giuliano S, Giulivi C, Giuriato S, Giustiniani J, Gluschko A, Goder V, Goginashvili A, Golab J, Goldstone DC, Golebiewska A, Gomes LR, Gomez R, Gómez-Sánchez R, Gomez-Puerto MC, Gomez-Sintes R, Gong Q, Goni FM, González-Gallego J, Gonzalez-Hernandez T, Gonzalez-Polo RA, Gonzalez-Reyes JA, González-Rodríguez P, Goping IS, Gorbatyuk MS, Gorbunov NV, Görgülü K, Gorojod RM, Gorski SM, Goruppi S, Gotor C, Gottlieb RA, Gozes I, Gozuacik D, Graef M, Gräler MH, Granatiero V, Grasso D, Gray JP, Green DR, Greenhough A, Gregory SL, Griffin EF, Grinstaff MW, Gros F, Grose C, Gross AS, Gruber F, Grumati P, Grune T, Gu X, Guan JL, Guardia CM, Guda K, Guerra F, Guerri C, Guha P, Guillén C, Gujar S, Gukovskaya A, Gukovsky I, Gunst J, Günther A, Guntur AR, Guo C, Guo C, Guo H, Guo LW, Guo M, Gupta P, Gupta SK, Gupta S, Gupta VB, Gupta V, Gustafsson AB, Gutterman DD, H B R, Haapasalo A, Haber JE, Hać A, Hadano S, Hafrén AJ, Haidar M, Hall BS, Halldén G, Hamacher-Brady A, Hamann A, Hamasaki M, Han W, Hansen M, Hanson PI, Hao Z, Harada M, Harhaji-Trajkovic L, Hariharan N, Haroon N, Harris J, Hasegawa T, Hasima Nagoor N, Haspel JA, Haucke V, Hawkins WD, Hay BA, Haynes CM, Hayrabedyan SB, Hays TS, He C, He Q, He RR, He YW, He YY, Heakal Y, Heberle AM, Hejtmancik JF, Helgason GV, Henkel V, Herb M, Hergovich A, Herman-Antosiewicz A, Hernández A, Hernandez C, Hernandez-Diaz S, Hernandez-Gea V, Herpin A, Herreros J, Hervás JH, Hesselson D, Hetz C, Heussler VT, Higuchi Y, Hilfiker S, Hill JA, Hlavacek WS, Ho EA, Ho IHT, Ho PW, Ho SL, Ho WY, Hobbs GA, Hochstrasser M, Hoet PHM, Hofius D, Hofman P, Höhn A, Holmberg CI, Hombrebueno JR, Yi-Ren Hong CH, Hooper LV, Hoppe T, Horos R, Hoshida Y, Hsin IL, Hsu HY, Hu B, Hu D, Hu LF, Hu MC, Hu R, Hu W, Hu YC, Hu ZW, Hua F, Hua J, Hua Y, Huan C, Huang C, Huang C, Huang C, Huang C, Huang H, Huang K, Huang MLH, Huang R, Huang S, Huang T, Huang X, Huang YJ, Huber TB, Hubert V, Hubner CA, Hughes SM, Hughes WE, Humbert M, Hummer G, Hurley JH, Hussain S, Hussain S, Hussey PJ, Hutabarat M, Hwang HY, Hwang S, Ieni A, Ikeda F, Imagawa Y, Imai Y, Imbriano C, Imoto M, Inman DM, Inoki K, Iovanna J, Iozzo RV, Ippolito G, Irazoqui JE, Iribarren P, Ishaq M, Ishikawa M, Ishimwe N, Isidoro C, Ismail N, Issazadeh-Navikas S, Itakura E, Ito D, Ivankovic D, Ivanova S, Iyer AKV, Izquierdo JM, Izumi M, Jäättelä M, Jabir MS, Jackson WT, Jacobo-Herrera N, Jacomin AC, Jacquin E, Jadiya P, Jaeschke H, Jagannath C, Jakobi AJ, Jakobsson J, Janji B, Jansen-Dürr P, Jansson PJ, Jantsch J, Januszewski S, Jassey A, Jean S, Jeltsch-David H, Jendelova P, Jenny A, Jensen TE, Jessen N, Jewell JL, Ji J, Jia L, Jia R, Jiang L, Jiang Q, Jiang R, Jiang T, Jiang X, Jiang Y, Jimenez-Sanchez M, Jin EJ, Jin F, Jin H, Jin L, Jin L, Jin M, Jin S, Jo EK, Joffre C, Johansen T, Johnson GVW, Johnston SA, Jokitalo E, Jolly MK, Joosten LAB, Jordan J, Joseph B, Ju D, Ju JS, Ju J, Juárez E, Judith D, Juhász G, Jun Y, Jung CH, Jung SC, Jung YK, Jungbluth H, Jungverdorben J, Just S, Kaarniranta K, Kaasik A, Kabuta T, Kaganovich D, Kahana A, Kain R, Kajimura S, Kalamvoki M, Kalia M, Kalinowski DS, Kaludercic N, Kalvari I, Kaminska J, Kaminskyy VO, Kanamori H, Kanasaki K, Kang C, Kang R, Kang SS, Kaniyappan S, Kanki T, Kanneganti TD, Kanthasamy AG, Kanthasamy A, Kantorow M, Kapuy O, Karamouzis MV, Karim MR, Karmakar P, Katare RG, Kato M, Kaufmann SHE, Kauppinen A, Kaushal GP, Kaushik S, Kawasaki K, Kazan K, Ke PY, Keating DJ, Keber U, Kehrl JH, Keller KE, Keller CW, Kemper JK, Kenific CM, Kepp O, Kermorgant S, Kern A, Ketteler R, Keulers TG, Khalfin B, Khalil H, Khambu B, Khan SY, Khandelwal VKM, Khandia R, Kho W, Khobrekar NV, Khuansuwan S, Khundadze M, Killackey SA, Kim D, Kim DR, Kim DH, Kim DE, Kim EY, Kim EK, Kim HR, Kim HS, Hyung-Ryong Kim , Kim JH, Kim JK, Kim JH, Kim J, Kim JH, Kim KI, Kim PK, Kim SJ, Kimball SR, Kimchi A, Kimmelman AC, Kimura T, King MA, Kinghorn KJ, Kinsey CG, Kirkin V, Kirshenbaum LA, Kiselev SL, Kishi S, Kitamoto K, Kitaoka Y, Kitazato K, Kitsis RN, Kittler JT, Kjaerulff O, Klein PS, Klopstock T, Klucken J, Knævelsrud H, Knorr RL, Ko BCB, Ko F, Ko JL, Kobayashi H, Kobayashi S, Koch I, Koch JC, Koenig U, Kögel D, Koh YH, Koike M, Kohlwein SD, Kocaturk NM, Komatsu M, König J, Kono T, Kopp BT, Korcsmaros T, Korkmaz G, Korolchuk VI, Korsnes MS, Koskela A, Kota J, Kotake Y, Kotler ML, Kou Y, Koukourakis MI, Koustas E, Kovacs AL, Kovács T, Koya D, Kozako T, Kraft C, Krainc D, Krämer H, Krasnodembskaya AD, Kretz-Remy C, Kroemer G, Ktistakis NT, Kuchitsu K, Kuenen S, Kuerschner L, Kukar T, Kumar A, Kumar A, Kumar D, Kumar D, Kumar S, Kume S, Kumsta C, Kundu CN, Kundu M, Kunnumakkara AB, Kurgan L, Kutateladze TG, Kutlu O, Kwak S, Kwon HJ, Kwon TK, Kwon YT, Kyrmizi I, La Spada A, Labonté P, Ladoire S, Laface I, Lafont F, Lagace DC, Lahiri V, Lai Z, Laird AS, Lakkaraju A, Lamark T, Lan SH, Landajuela A, Lane DJR, Lane JD, Lang CH, Lange C, Langel Ü, Langer R, Lapaquette P, Laporte J, LaRusso NF, Lastres-Becker I, Lau WCY, Laurie GW, Lavandero S, Law BYK, Law HK, Layfield R, Le W, Le Stunff H, Leary AY, Lebrun JJ, Leck LYW, Leduc-Gaudet JP, Lee C, Lee CP, Lee DH, Lee EB, Lee EF, Lee GM, Lee HJ, Lee HK, Lee JM, Lee JS, Lee JA, Lee JY, Lee JH, Lee M, Lee MG, Lee MJ, Lee MS, Lee SY, Lee SJ, Lee SY, Lee SB, Lee WH, Lee YR, Lee YH, Lee Y, Lefebvre C, Legouis R, Lei YL, Lei Y, Leikin S, Leitinger G, Lemus L, Leng S, Lenoir O, Lenz G, Lenz HJ, Lenzi P, León Y, Leopoldino AM, Leschczyk C, Leskelä S, Letellier E, Leung CT, Leung PS, Leventhal JS, Levine B, Lewis PA, Ley K, Li B, Li DQ, Li J, Li J, Li J, Li K, Li L, Li M, Li M, Li M, Li M, Li M, Li PL, Li MQ, Li Q, Li S, Li T, Li W, Li W, Li X, Li YP, Li Y, Li Z, Li Z, Li Z, Lian J, Liang C, Liang Q, Liang W, Liang Y, Liang Y, Liao G, Liao L, Liao M, Liao YF, Librizzi M, Lie PPY, Lilly MA, Lim HJ, Lima TRR, Limana F, Lin C, Lin CW, Lin DS, Lin FC, Lin JD, Lin KM, Lin KH, Lin LT, Lin PH, Lin Q, Lin S, Lin SJ, Lin W, Lin X, Lin YX, Lin YS, Linden R, Lindner P, Ling SC, Lingor P, Linnemann AK, Liou YC, Lipinski MM, Lipovšek S, Lira VA, Lisiak N, Liton PB, Liu C, Liu CH, Liu CF, Liu CH, Liu F, Liu H, Liu HS, Liu HF, Liu H, Liu J, Liu J, Liu J, Liu L, Liu L, Liu M, Liu Q, Liu W, Liu W, Liu XH, Liu X, Liu X, Liu X, Liu X, Liu Y, Liu Y, Liu Y, Liu Y, Liu Y, Livingston JA, Lizard G, Lizcano JM, Ljubojevic-Holzer S, LLeonart ME, Llobet-Navàs D, Llorente A, Lo CH, Lobato-Márquez D, Long Q, Long YC, Loos B, Loos JA, López MG, López-Doménech G, López-Guerrero JA, López-Jiménez AT, López-Pérez Ó, López-Valero I, Lorenowicz MJ, Lorente M, Lorincz P, Lossi L, Lotersztajn S, Lovat PE, Lovell JF, Lovy A, Lőw P, Lu G, Lu H, Lu JH, Lu JJ, Lu M, Lu S, Luciani A, Lucocq JM, Ludovico P, Luftig MA, Luhr M, Luis-Ravelo D, Lum JJ, Luna-Dulcey L, Lund AH, Lund VK, Lünemann JD, Lüningschrör P, Luo H, Luo R, Luo S, Luo Z, Luparello C, Lüscher B, Luu L, Lyakhovich A, Lyamzaev KG, Lystad AH, Lytvynchuk L, Ma AC, Ma C, Ma M, Ma NF, Ma QH, Ma X, Ma Y, Ma Z, MacDougald OA, Macian F, MacIntosh GC, MacKeigan JP, Macleod KF, Maday S, Madeo F, Madesh M, Madl T, Madrigal-Matute J, Maeda A, Maejima Y, Magarinos M, Mahavadi P, Maiani E, Maiese K, Maiti P, Maiuri MC, Majello B, Major MB, Makareeva E, Malik F, Mallilankaraman K, Malorni W, Maloyan A, Mammadova N, Man GCW, Manai F, Mancias JD, Mandelkow EM, Mandell MA, Manfredi AA, Manjili MH, Manjithaya R, Manque P, Manshian BB, Manzano R, Manzoni C, Mao K, Marchese C, Marchetti S, Marconi AM, Marcucci F, Mardente S, Mareninova OA, Margeta M, Mari M, Marinelli S, Marinelli O, Mariño G, Mariotto S, Marshall RS, Marten MR, Martens S, Martin APJ, Martin KR, Martin S, Martin S, Martín-Segura A, Martín-Acebes MA, Martin-Burriel I, Martin-Rincon M, Martin-Sanz P, Martina JA, Martinet W, Martinez A, Martinez A, Martinez J, Martinez Velazquez M, Martinez-Lopez N, Martinez-Vicente M, Martins DO, Martins JO, Martins WK, Martins-Marques T, Marzetti E, Masaldan S, Masclaux-Daubresse C, Mashek DG, Massa V, Massieu L, Masson GR, Masuelli L, Masyuk AI, Masyuk TV, Matarrese P, Matheu A, Matoba S, Matsuzaki S, Mattar P, Matte A, Mattoscio D, Mauriz JL, Mauthe M, Mauvezin C, Maverakis E, Maycotte P, Mayer J, Mazzoccoli G, Mazzoni C, Mazzulli JR, McCarty N, McDonald C, McGill MR, McKenna SL, McLaughlin B, McLoughlin F, McNiven MA, McWilliams TG, Mechta-Grigoriou F, Medeiros TC, Medina DL, Megeney LA, Megyeri K, Mehrpour M, Mehta JL, Meijer AJ, Meijer AH, Mejlvang J, Meléndez A, Melk A, Memisoglu G, Mendes AF, Meng D, Meng F, Meng T, Menna-Barreto R, Menon MB, Mercer C, Mercier AE, Mergny JL, Merighi A, Merkley SD, Merla G, Meske V, Mestre AC, Metur SP, Meyer C, Meyer H, Mi W, Mialet-Perez J, Miao J, Micale L, Miki Y, Milan E, Milczarek M, Miller DL, Miller SI, Miller S, Millward SW, Milosevic I, Minina EA, Mirzaei H, Mirzaei HR, Mirzaei M, Mishra A, Mishra N, Mishra PK, Misirkic Marjanovic M, Misasi R, Misra A, Misso G, Mitchell C, Mitou G, Miura T, Miyamoto S, Miyazaki M, Miyazaki M, Miyazaki T, Miyazawa K, Mizushima N, Mogensen TH, Mograbi B, Mohammadinejad R, Mohamud Y, Mohanty A, Mohapatra S, Möhlmann T, Mohmmed A, Moles A, Moley KH, Molinari M, Mollace V, Møller AB, Mollereau B, Mollinedo F, Montagna C, Monteiro MJ, Montella A, Montes LR, Montico B, Mony VK, Monzio Compagnoni G, Moore MN, Moosavi MA, Mora AL, Mora M, Morales-Alamo D, Moratalla R, Moreira PI, Morelli E, Moreno S, Moreno-Blas D, Moresi V, Morga B, Morgan AH, Morin F, Morishita H, Moritz OL, Moriyama M, Moriyasu Y, Morleo M, Morselli E, Moruno-Manchon JF, Moscat J, Mostowy S, Motori E, Moura AF, Moustaid-Moussa N, Mrakovcic M, Muciño-Hernández G, Mukherjee A, Mukhopadhyay S, Mulcahy Levy JM, Mulero V, Muller S, Münch C, Munjal A, Munoz-Canoves P, Muñoz-Galdeano T, Münz C, Murakawa T, Muratori C, Murphy BM, Murphy JP, Murthy A, Myöhänen TT, Mysorekar IU, Mytych J, Nabavi SM, Nabissi M, Nagy P, Nah J, Nahimana A, Nakagawa I, Nakamura K, Nakatogawa H, Nandi SS, Nanjundan M, Nanni M, Napolitano G, Nardacci R, Narita M, Nassif M, Nathan I, Natsumeda M, Naude RJ, Naumann C, Naveiras O, Navid F, Nawrocki ST, Nazarko TY, Nazio F, Negoita F, Neill T, Neisch AL, Neri LM, Netea MG, Neubert P, Neufeld TP, Neumann D, Neutzner A, Newton PT, Ney PA, Nezis IP, Ng CCW, Ng TB, Nguyen HTT, Nguyen LT, Ni HM, Ní Cheallaigh C, Ni Z, Nicolao MC, Nicoli F, Nieto-Diaz M, Nilsson P, Ning S, Niranjan R, Nishimune H, Niso-Santano M, Nixon RA, Nobili A, Nobrega C, Noda T, Nogueira-Recalde U, Nolan TM, Nombela I, Novak I, Novoa B, Nozawa T, Nukina N, Nussbaum-Krammer C, Nylandsted J, O'Donovan TR, O'Leary SM, O'Rourke EJ, O'Sullivan MP, O'Sullivan TE, Oddo S, Oehme I, Ogawa M, Ogier-Denis E, Ogmundsdottir MH, Ogretmen B, Oh GT, Oh SH, Oh YJ, Ohama T, Ohashi Y, Ohmuraya M, Oikonomou V, Ojha R, Okamoto K, Okazawa H, Oku M, Oliván S, Oliveira JMA, Ollmann M, Olzmann JA, Omari S, Omary MB, Önal G, Ondrej M, Ong SB, Ong SG, Onnis A, Orellana JA, Orellana-Muñoz S, Ortega-Villaizan MDM, Ortiz-Gonzalez XR, Ortona E, Osiewacz HD, Osman AK, Osta R, Otegui MS, Otsu K, Ott C, Ottobrini L, Ou JJ, Outeiro TF, Oynebraten I, Ozturk M, Pagès G, Pahari S, Pajares M, Pajvani UB, Pal R, Paladino S, Pallet N, Palmieri M, Palmisano G, Palumbo C, Pampaloni F, Pan L, Pan Q, Pan W, Pan X, Panasyuk G, Pandey R, Pandey UB, Pandya V, Paneni F, Pang SY, Panzarini E, Papademetrio DL, Papaleo E, Papinski D, Papp D, Park EC, Park HT, Park JM, Park JI, Park JT, Park J, Park SC, Park SY, Parola AH, Parys JB, Pasquier A, Pasquier B, Passos JF, Pastore N, Patel HH, Patschan D, Pattingre S, Pedraza-Alva G, Pedraza-Chaverri J, Pedrozo Z, Pei G, Pei J, Peled-Zehavi H, Pellegrini JM, Pelletier J, Peñalva MA, Peng D, Peng Y, Penna F, Pennuto M, Pentimalli F, Pereira CM, Pereira GJS, Pereira LC, Pereira de Almeida L, Perera ND, Pérez-Lara Á, Perez-Oliva AB, Pérez-Pérez ME, Periyasamy P, Perl A, Perrotta C, Perrotta I, Pestell RG, Petersen M, Petrache I, Petrovski G, Pfirrmann T, Pfister AS, Philips JA, Pi H, Picca A, Pickrell AM, Picot S, Pierantoni GM, Pierdominici M, Pierre P, Pierrefite-Carle V, Pierzynowska K, Pietrocola F, Pietruczuk M, Pignata C, Pimentel-Muiños FX, Pinar M, Pinheiro RO, Pinkas-Kramarski R, Pinton P, Pircs K, Piya S, Pizzo P, Plantinga TS, Platta HW, Plaza-Zabala A, Plomann M, Plotnikov EY, Plun-Favreau H, Pluta R, Pocock R, Pöggeler S, Pohl C, Poirot M, Poletti A, Ponpuak M, Popelka H, Popova B, Porta H, Porte Alcon S, Portilla-Fernandez E, Post M, Potts MB, Poulton J, Powers T, Prahlad V, Prajsnar TK, Praticò D, Prencipe R, Priault M, Proikas-Cezanne T, Promponas VJ, Proud CG, Puertollano R, Puglielli L, Pulinilkunnil T, Puri D, Puri R, Puyal J, Qi X, Qi Y, Qian W, Qiang L, Qiu Y, Quadrilatero J, Quarleri J, Raben N, Rabinowich H, Ragona D, Ragusa MJ, Rahimi N, Rahmati M, Raia V, Raimundo N, Rajasekaran NS, Ramachandra Rao S, Rami A, Ramírez-Pardo I, Ramsden DB, Randow F, Rangarajan PN, Ranieri D, Rao H, Rao L, Rao R, Rathore S, Ratnayaka JA, Ratovitski EA, Ravanan P, Ravegnini G, Ray SK, Razani B, Rebecca V, Reggiori F, Régnier-Vigouroux A, Reichert AS, Reigada D, Reiling JH, Rein T, Reipert S, Rekha RS, Ren H, Ren J, Ren W, Renault T, Renga G, Reue K, Rewitz K, Ribeiro de Andrade Ramos B, Riazuddin SA, Ribeiro-Rodrigues TM, Ricci JE, Ricci R, Riccio V, Richardson DR, Rikihisa Y, Risbud MV, Risueño RM, Ritis K, Rizza S, Rizzuto R, Roberts HC, Roberts LD, Robinson KJ, Roccheri MC, Rocchi S, Rodney GG, Rodrigues T, Rodrigues Silva VR, Rodriguez A, Rodriguez-Barrueco R, Rodriguez-Henche N, Rodriguez-Rocha H, Roelofs J, Rogers RS, Rogov VV, Rojo AI, Rolka K, Romanello V, Romani L, Romano A, Romano PS, Romeo-Guitart D, Romero LC, Romero M, Roney JC, Rongo C, Roperto S, Rosenfeldt MT, Rosenstiel P, Rosenwald AG, Roth KA, Roth L, Roth S, Rouschop KMA, Roussel BD, Roux S, Rovere-Querini P, Roy A, Rozieres A, Ruano D, Rubinsztein DC, Rubtsova MP, Ruckdeschel K, Ruckenstuhl C, Rudolf E, Rudolf R, Ruggieri A, Ruparelia AA, Rusmini P, Russell RR, Russo GL, Russo M, Russo R, Ryabaya OO, Ryan KM, Ryu KY, Sabater-Arcis M, Sachdev U, Sacher M, Sachse C, Sadhu A, Sadoshima J, Safren N, Saftig P, Sagona AP, Sahay G, Sahebkar A, Sahin M, Sahin O, Sahni S, Saito N, Saito S, Saito T, Sakai R, Sakai Y, Sakamaki JI, Saksela K, Salazar G, Salazar-Degracia A, Salekdeh GH, Saluja AK, Sampaio-Marques B, Sanchez MC, Sanchez-Alcazar JA, Sanchez-Vera V, Sancho-Shimizu V, Sanderson JT, Sandri M, Santaguida S, Santambrogio L, Santana MM, Santoni G, Sanz A, Sanz P, Saran S, Sardiello M, Sargeant TJ, Sarin A, Sarkar C, Sarkar S, Sarrias MR, Sarkar S, Sarmah DT, Sarparanta J, Sathyanarayan A, Sathyanarayanan R, Scaglione KM, Scatozza F, Schaefer L, Schafer ZT, Schaible UE, Schapira AHV, Scharl M, Schatzl HM, Schein CH, Scheper W, Scheuring D, Schiaffino MV, Schiappacassi M, Schindl R, Schlattner U, Schmidt O, Schmitt R, Schmidt SD, Schmitz I, Schmukler E, Schneider A, Schneider BE, Schober R, Schoijet AC, Schott MB, Schramm M, Schröder B, Schuh K, Schüller C, Schulze RJ, Schürmanns L, Schwamborn JC, Schwarten M, Scialo F, Sciarretta S, Scott MJ, Scotto KW, Scovassi AI, Scrima A, Scrivo A, Sebastian D, Sebti S, Sedej S, Segatori L, Segev N, Seglen PO, Seiliez I, Seki E, Selleck SB, Sellke FW, Selsby JT, Sendtner M, Senturk S, Seranova E, Sergi C, Serra-Moreno R, Sesaki H, Settembre C, Setty SRG, Sgarbi G, Sha O, Shacka JJ, Shah JA, Shang D, Shao C, Shao F, Sharbati S, Sharkey LM, Sharma D, Sharma G, Sharma K, Sharma P, Sharma S, Shen HM, Shen H, Shen J, Shen M, Shen W, Shen Z, Sheng R, Sheng Z, Sheng ZH, Shi J, Shi X, Shi YH, Shiba-Fukushima K, Shieh JJ, Shimada Y, Shimizu S, Shimozawa M, Shintani T, Shoemaker CJ, Shojaei S, Shoji I, Shravage BV, Shridhar V, Shu CW, Shu HB, Shui K, Shukla AK, Shutt TE, Sica V, Siddiqui A, Sierra A, Sierra-Torre V, Signorelli S, Sil P, Silva BJA, Silva JD, Silva-Pavez E, Silvente-Poirot S, Simmonds RE, Simon AK, Simon HU, Simons M, Singh A, Singh LP, Singh R, Singh SV, Singh SK, Singh SB, Singh S, Singh SP, Sinha D, Sinha RA, Sinha S, Sirko A, Sirohi K, Sivridis EL, Skendros P, Skirycz A, Slaninová I, Smaili SS, Smertenko A, Smith MD, Soenen SJ, Sohn EJ, Sok SPM, Solaini G, Soldati T, Soleimanpour SA, Soler RM, Solovchenko A, Somarelli JA, Sonawane A, Song F, Song HK, Song JX, Song K, Song Z, Soria LR, Sorice M, Soukas AA, Soukup SF, Sousa D, Sousa N, Spagnuolo PA, Spector SA, Srinivas Bharath MM, St Clair D, Stagni V, Staiano L, Stalnecker CA, Stankov MV, Stathopulos PB, Stefan K, Stefan SM, Stefanis L, Steffan JS, Steinkasserer A, Stenmark H, Sterneckert J, Stevens C, Stoka V, Storch S, Stork B, Strappazzon F, Strohecker AM, Stupack DG, Su H, Su LY, Su L, Suarez-Fontes AM, Subauste CS, Subbian S, Subirada PV, Sudhandiran G, Sue CM, Sui X, Summers C, Sun G, Sun J, Sun K, Sun MX, Sun Q, Sun Y, Sun Z, Sunahara KKS, Sundberg E, Susztak K, Sutovsky P, Suzuki H, Sweeney G, Symons JD, Sze SCW, Szewczyk NJ, Tabęcka-Łonczynska A, Tabolacci C, Tacke F, Taegtmeyer H, Tafani M, Tagaya M, Tai H, Tait SWG, Takahashi Y, Takats S, Talwar P, Tam C, Tam SY, Tampellini D, Tamura A, Tan CT, Tan EK, Tan YQ, Tanaka M, Tanaka M, Tang D, Tang J, Tang TS, Tanida I, Tao Z, Taouis M, Tatenhorst L, Tavernarakis N, Taylor A, Taylor GA, Taylor JM, Tchetina E, Tee AR, Tegeder I, Teis D, Teixeira N, Teixeira-Clerc F, Tekirdag KA, Tencomnao T, Tenreiro S, Tepikin AV, Testillano PS, Tettamanti G, Tharaux PL, Thedieck K, Thekkinghat AA, Thellung S, Thinwa JW, Thirumalaikumar VP, Thomas SM, Thomes PG, Thorburn A, Thukral L, Thum T, Thumm M, Tian L, Tichy A, Till A, Timmerman V, Titorenko VI, Todi SV, Todorova K, Toivonen JM, Tomaipitinca L, Tomar D, Tomas-Zapico C, Tomić S, Tong BC, Tong C, Tong X, Tooze SA, Torgersen ML, Torii S, Torres-López L, Torriglia A, Towers CG, Towns R, Toyokuni S, Trajkovic V, Tramontano D, Tran QG, Travassos LH, Trelford CB, Tremel S, Trougakos IP, Tsao BP, Tschan MP, Tse HF, Tse TF, Tsugawa H, Tsvetkov AS, Tumbarello DA, Tumtas Y, Tuñón MJ, Turcotte S, Turk B, Turk V, Turner BJ, Tuxworth RI, Tyler JK, Tyutereva EV, Uchiyama Y, Ugun-Klusek A, Uhlig HH, Ułamek-Kozioł M, Ulasov IV, Umekawa M, Ungermann C, Unno R, Urbe S, Uribe-Carretero E, Üstün S, Uversky VN, Vaccari T, Vaccaro MI, Vahsen BF, Vakifahmetoglu-Norberg H, Valdor R, Valente MJ, Valko A, Vallee RB, Valverde AM, Van den Berghe G, van der Veen S, Van Kaer L, van Loosdregt J, van Wijk SJL, Vandenberghe W, Vanhorebeek I, Vannier-Santos MA, Vannini N, Vanrell MC, Vantaggiato C, Varano G, Varela-Nieto I, Varga M, Vasconcelos MH, Vats S, Vavvas DG, Vega-Naredo I, Vega-Rubin-de-Celis S, Velasco G, Velázquez AP, Vellai T, Vellenga E, Velotti F, Verdier M, Verginis P, Vergne I, Verkade P, Verma M, Verstreken P, Vervliet T, Vervoorts J, Vessoni AT, Victor VM, Vidal M, Vidoni C, Vieira OV, Vierstra RD, Viganó S, Vihinen H, Vijayan V, Vila M, Vilar M, Villalba JM, Villalobo A, Villarejo-Zori B, Villarroya F, Villarroya J, Vincent O, Vindis C, Viret C, Viscomi MT, Visnjic D, Vitale I, Vocadlo DJ, Voitsekhovskaja OV, Volonté C, Volta M, Vomero M, Von Haefen C, Vooijs MA, Voos W, Vucicevic L, Wade-Martins R, Waguri S, Waite KA, Wakatsuki S, Walker DW, Walker MJ, Walker SA, Walter J, Wandosell FG, Wang B, Wang CY, Wang C, Wang C, Wang C, Wang CY, Wang D, Wang F, Wang F, Wang F, Wang G, Wang H, Wang H, Wang H, Wang HG, Wang J, Wang J, Wang J, Wang J, Wang K, Wang L, Wang L, Wang MH, Wang M, Wang N, Wang P, Wang P, Wang P, Wang P, Wang QJ, Wang Q, Wang QK, Wang QA, Wang WT, Wang W, Wang X, Wang X, Wang Y, Wang Y, Wang Y, Wang YY, Wang Y, Wang Y, Wang Y, Wang Y, Wang Z, Wang Z, Wang Z, Warnes G, Warnsmann V, Watada H, Watanabe E, Watchon M, Wawrzyńska A, Weaver TE, Wegrzyn G, Wehman AM, Wei H, Wei L, Wei T, Wei Y, Weiergräber OH, Weihl CC, Weindl G, Weiskirchen R, Wells A, Wen RH, Wen X, Werner A, Weykopf B, Wheatley SP, Whitton JL, Whitworth AJ, Wiktorska K, Wildenberg ME, Wileman T, Wilkinson S, Willbold D, Williams B, Williams RSB, Williams RL, Williamson PR, Wilson RA, Winner B, Winsor NJ, Witkin SS, Wodrich H, Woehlbier U, Wollert T, Wong E, Wong JH, Wong RW, Wong VKW, Wong WW, Wu AG, Wu C, Wu J, Wu J, Wu KK, Wu M, Wu SY, Wu S, Wu SY, Wu S, Wu WKK, Wu X, Wu X, Wu YW, Wu Y, Xavier RJ, Xia H, Xia L, Xia Z, Xiang G, Xiang J, Xiang M, Xiang W, Xiao B, Xiao G, Xiao H, Xiao HT, Xiao J, Xiao L, Xiao S, Xiao Y, Xie B, Xie CM, Xie M, Xie Y, Xie Z, Xie Z, Xilouri M, Xu C, Xu E, Xu H, Xu J, Xu J, Xu L, Xu WW, Xu X, Xue Y, Yakhine-Diop SMS, Yamaguchi M, Yamaguchi O, Yamamoto A, Yamashina S, Yan S, Yan SJ, Yan Z, Yanagi Y, Yang C, Yang DS, Yang H, Yang HT, Yang H, Yang JM, Yang J, Yang J, Yang L, Yang L, Yang M, Yang PM, Yang Q, Yang S, Yang S, Yang SF, Yang W, Yang WY, Yang X, Yang X, Yang Y, Yang Y, Yao H, Yao S, Yao X, Yao YG, Yao YM, Yasui T, Yazdankhah M, Yen PM, Yi C, Yin XM, Yin Y, Yin Z, Yin Z, Ying M, Ying Z, Yip CK, Yiu SPT, Yoo YH, Yoshida K, Yoshii SR, Yoshimori T, Yousefi B, Yu B, Yu H, Yu J, Yu J, Yu L, Yu ML, Yu SW, Yu VC, Yu WH, Yu Z, Yu Z, Yuan J, Yuan LQ, Yuan S, Yuan SF, Yuan Y, Yuan Z, Yue J, Yue Z, Yun J, Yung RL, Zacks DN, Zaffagnini G, Zambelli VO, Zanella I, Zang QS, Zanivan S, Zappavigna S, Zaragoza P, Zarbalis KS, Zarebkohan A, Zarrouk A, Zeitlin SO, Zeng J, Zeng JD, Žerovnik E, Zhan L, Zhang B, Zhang DD, Zhang H, Zhang H, Zhang H, Zhang H, Zhang H, Zhang H, Zhang H, Zhang HL, Zhang J, Zhang J, Zhang JP, Zhang KYB, Zhang LW, Zhang L, Zhang L, Zhang L, Zhang L, Zhang M, Zhang P, Zhang S, Zhang W, Zhang X, Zhang XW, Zhang X, Zhang X, Zhang X, Zhang X, Zhang XD, Zhang Y, Zhang Y, Zhang Y, Zhang YD, Zhang Y, Zhang YY, Zhang Y, Zhang Z, Zhang Z, Zhang Z, Zhang Z, Zhang Z, Zhang Z, Zhao H, Zhao L, Zhao S, Zhao T, Zhao XF, Zhao Y, Zhao Y, Zhao Y, Zhao Y, Zheng G, Zheng K, Zheng L, Zheng S, Zheng XL, Zheng Y, Zheng ZG, Zhivotovsky B, Zhong Q, Zhou A, Zhou B, Zhou C, Zhou G, Zhou H, Zhou H, Zhou H, Zhou J, Zhou J, Zhou J, Zhou J, Zhou K, Zhou R, Zhou XJ, Zhou Y, Zhou Y, Zhou Y, Zhou ZY, Zhou Z, Zhu B, Zhu C, Zhu GQ, Zhu H, Zhu H, Zhu H, Zhu WG, Zhu Y, Zhu Y, Zhuang H, Zhuang X, Zientara-Rytter K, Zimmermann CM, Ziviani E, Zoladek T, Zong WX, Zorov DB, Zorzano A, Zou W, Zou Z, Zou Z, Zuryn S, Zwerschke W, Brand-Saberi B, Dong XC, Kenchappa CS, Li Z, Lin Y, Oshima S, Rong Y, Sluimer JC, Stallings CL, Tong CK.
      In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
    Keywords:  Autophagosome; LC3; cancer; flux; lysosome; macroautophagy; neurodegeneration; phagophore; stress; vacuole