bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2024‒04‒21
fifteen papers selected by
Lakesh Kumar, BITS Pilani
  1. The α subunit of AMP-activated protein kinase is critical for the metabolic success and tachyzoite proliferation of Toxoplasma gondii.
  2. Inhibition of Foxp3 expression in the placenta of mice infected intraperitoneally by toxoplasma gondii tachyzoites: insights into the PPARγ/miR-7b-5p/Sp1 signaling pathway.
  3. Apicomplexa micropore: history, function, and formation.
  4. Contribution of microscopy to a better understanding of the anatomy of pathogenic protists.
  5. Molecular Regulation of NLRP3 Inflammasome Activation During Parasitic Infection.
  6. Deciphering the epidemiological dynamics: Toxoplasma gondii seroprevalence in mainland China's food animals, 2010-2023.
  7. Mitochondrial energy state controls AMPK-mediated foraging behavior in C. elegans.
  8. ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and regulates the Warburg effect in breast cancer.
  9. Molecular dynamics simulations of intracellular lipid droplets: a new tool in the toolbox.
  10. Effect of concurrent infection of Helicobacter pylori with Toxoplasma gondii infection on gastric pathology.
  11. Current trends in clinical trials and the development of small molecule epigenetic inhibitors as cancer therapeutics.
  12. Deciphering the interplay of histone post-translational modifications in cancer: Co-targeting histone modulators for precision therapy.
  13. ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA.
  14. Class I histone deacetylases inhibition reverses memory impairment induced by acute stress in mice.
  15. Energy deprivation-induced autophagy and aggrephagy: insights from yeast and mammals.
  1. Microb Biotechnol. 2024 Apr;17(4): e14455
    The α subunit of AMP-activated protein kinase is critical for the metabolic success and tachyzoite proliferation of Toxoplasma gondii.
    Xuke Yang, Jichao Yang, Mengyu Lyu, Yaqiong Li, Anqi Liu, Bang Shen.
      Toxoplasma gondii is a zoonotic parasite infecting humans and nearly all warm-blooded animals. Successful parasitism in diverse hosts at various developmental stages requires the parasites to fine tune their metabolism according to environmental cues and the parasite's needs. By manipulating the β and γ subunits, we have previously shown that AMP-activated protein kinase (AMPK) has critical roles in regulating the metabolic and developmental programmes. However, the biological functions of the α catalytic subunit have not been established. T. gondii encodes a canonical AMPKα, as well as a KIN kinase whose kinase domain has high sequence similarities to those of classic AMPKα proteins. Here, we found that TgKIN is dispensable for tachyzoite growth, whereas TgAMPKα is essential. Depletion of TgAMPKα expression resulted in decreased ATP levels and reduced metabolic flux in glycolysis and the tricarboxylic acid cycle, confirming that TgAMPK is involved in metabolic regulation and energy homeostasis in the parasite. Sequential truncations at the C-terminus found an α-helix that is key for the function of TgAMPKα. The amino acid sequences of this α-helix are not conserved among various AMPKα proteins, likely because it is involved in interactions with TgAMPKβ, which only have limited sequence similarities to AMPKβ in other eukaryotes. The essential role of the less conserved C-terminus of TgAMPKα provides opportunities for parasite specific drug designs targeting TgAMPKα.
    DOI:  https://doi.org/10.1111/1751-7915.14455
  2. Parasit Vectors. 2024 Apr 17. 17(1): 189
    Inhibition of Foxp3 expression in the placenta of mice infected intraperitoneally by toxoplasma gondii tachyzoites: insights into the PPARγ/miR-7b-5p/Sp1 signaling pathway.
    Yue Zhong, Cheng Qin, Qing Wang, Maoyuan Ding, Chong Qiu, Yunzhao Xu, Jinling Chen.
      BACKGROUND: Toxoplasma gondii, an obligate intracellular parasitic protozoa, infects approximately 30% of the global population. Contracting T. gondii at the primary infection of the mother can result in neonatal microcephaly, chorioretinitis, hydrocephalus, or mortality. Our previous study indicated that pregnant mice infected with T. gondii displayed a decrease in both the number and the suppressive ability of regulatory T cells, accompanied by the reduced Forkhead box P3 (Foxp3). Numerous studies have proved that microRNAs (miRNAs) are implicated in T. gondii infection, but there is meager evidence on the relationship between alterations of miRNAs and downregulation of Foxp3 induced by T. gondii.METHODS: Quantitative reverse transcription polymerase chain reaction was utilized to detect the transcriptions of miRNAs and Foxp3. Protein blotting and immunofluorescence were used to detect the expressions of Foxp3 and related transcription factors. The structure of mouse placenta was observed by hematoxylin and eosin (HE) staining. To examine the activity of miR-7b promoter and whether miR-7b-5p targets Sp1 to suppress Foxp3 expression, we constructed recombinant plasmids containing the full-length/truncated/mutant miR-7b promoter sequence or wildtype/mutant of Sp1 3' untranslated region (3' UTR) to detect the fluorescence activity in EL4 cells.
    RESULTS: In T. gondii-infected mice, miR-7b transcription was significantly elevated, while Foxp3 expression was decreased in the placenta. In vitro, miR-7b mimics downregulated Foxp3 expression, whereas its inhibitors significantly upregulated Foxp3 expression. miR-7b promoter activity was elevated upon the stimulation of T. gondii antigens, which was mitigated by co-transfection of mutant miR-7b promoter lacking peroxisome proliferator-activated receptor γ (PPARγ) target sites. Additionally, miR-7b mimics diminished Sp1 expression, while miR-7b inhibitors elevated its expression. miR-7b mimics deceased the fluorescence activity of Sp1 3' untranslated region (3' UTR), but it failed to impact the fluorescence activity upon the co-transfection of mutant Sp1 3' UTR lacking miR-7b target site.
    CONCLUSIONS: T. gondii infection and antigens promote miR-7b transcription but inhibit Foxp3 protein and gene levels. T. gondii antigens promote miR-7b promoter activity by a PPARγ-dependent mechanism. miR-7b directly binds to Sp1 3' UTR to repress Sp1 expression. Understanding the regulatory functions by which T. gondii-induced miR-7b suppresses Foxp3 expression can provide new perspectives for the possible therapeutic avenue of T. gondii-induced adverse pregnancy outcomes.
    Keywords:   Toxoplasma gondii ; Forkhead box P3; PPARγ; Sp1; microRNA-7b
    DOI:  https://doi.org/10.1186/s13071-024-06262-0
  3. Trends Parasitol. 2024 Apr 17. pii: S1471-4922(24)00079-5. [Epub ahead of print]
    Apicomplexa micropore: history, function, and formation.
    Jiong Yang, Shaojun Long, Geoff Hide, Zhao-Rong Lun, De-Hua Lai.
      The micropore, a mysterious structure found in apicomplexan species, was recently shown to be essential for nutrient acquisition in Plasmodium falciparum and Toxoplasma gondii. However, the differences between the micropores of these two parasites questions the nature of a general apicomplexan micropore structure and whether the formation process model from Plasmodium can be applied to other apicomplexans. We analyzed the literature on different apicomplexan micropores and found that T. gondii probably harbors a more representative micropore type than the more widely studied ones in Plasmodium. Using recent knowledge of the Kelch 13 (K13) protein interactome and gene depletion phenotypes in the T. gondii micropore, we propose a model of micropore formation, thus enriching our wider understanding of micropore protein function.
    Keywords:  Apicomplexa; EPS15; Kelch 13; formation model; micropore
    DOI:  https://doi.org/10.1016/j.pt.2024.03.008
  4. Proc Natl Acad Sci U S A. 2024 Apr 23. 121(17): e2321515121
    Contribution of microscopy to a better understanding of the anatomy of pathogenic protists.
    Wanderley de Souza.
      In this Inaugural Article the author briefly revises its scientific career and how he starts to work with parasitic protozoa. Emphasis is given to his contribution to topics such as a) the structural organization of the surface of protozoa using freeze-fracture and deep-etching; b) the cytoskeleton of protozoa, especially structures such as the subpellicular microtubules of trypanosomatids, the conoid of Toxoplasma gondii, microtubules and inner membrane complex of this protozoan, and the costa of Tritrichomonas foetus; c) the flagellulm of trypanosomatids, that in addition to the axoneme contains a complex network of filaments that constitute the paraflagellar rod; d) special organelles such as the acidocalcisome, hydrogenosome, and glycosome; and e) the highly polarized endocytic pathway found in epimastigote forms of Trypanosoma cruzi.
    Keywords:  cell surface; electron microscopy; endocytic pathway; parasitic protozoa; special organelles
    DOI:  https://doi.org/10.1073/pnas.2321515121
  5. Biosci Rep. 2024 Apr 16. pii: BSR20231918. [Epub ahead of print]
    Molecular Regulation of NLRP3 Inflammasome Activation During Parasitic Infection.
    Rasha Alonaizan.
      Parasitic diseases are a serious global health concern, causing many common and severe infections, including Chagas disease, leishmaniasis,and schistosomiasis. The NLRP3 inflammasome belongs to the NLR (nucleotide-binding domain leucine-rich-repeat-containing proteins) family, which are cytosolic proteins playing key roles in the detection of pathogens. NLRP3 inflammasomes are activated in immune responses to Plasmodium,Leishmania, Toxoplasma gondii, Entamoeba histolytica,Trypanosoma cruzi and other parasites. The role of NLRP3 is not fully understood, but it is a crucial component of the innate immune response to parasitic infections and its functions as a sensor triggering the inflammatory response to the invasive parasites. However, while this response can limit the parasites' growth, it can also result in potentially catastrophic host pathology. This makes it essential to understand how NLRP3 interacts with parasites to initiate the inflammatory response. Plasmodium hemozoin, Leishmania glycoconjugate lipophosphoglycan (LPG) and E. histolytica Gal/GalNAc lectin can stimulate NLRP3 activation, while the dense granule protein 9 (GRA9) of T. gondii has been shown to suppress it. Several other parasitic products also have diverse effects on NLRP3 activation. Understanding the mechanism of NLRP3 interaction with these products will help to develop advanced therapeutic approaches to treat parasitic diseases. This review summarizes current knowledge of the NLRP3 inflammasome's action on the immune response to parasitic infections and aims to determine the mechanisms through which parasitic molecules either activate or inhibit its action.
    Keywords:  Helminths; NLRP3 Inflammasomes; Plasmodium; T. gondii; Trypanosome cruzi
    DOI:  https://doi.org/10.1042/BSR20231918
  6. Front Cell Infect Microbiol. 2024 ;14 1381537
    Deciphering the epidemiological dynamics: Toxoplasma gondii seroprevalence in mainland China's food animals, 2010-2023.
    Zipeng Yang, Hao Yuan, Linchong Nie, Qingyuan Wen, Haoxin Li, Liulu Yang, Yining Song, Xun Luo, Xiu-Xiang Zhang, Zi-Guo Yuan.
      Background: Toxoplasma gondii (T. gondii) is a significant protozoan pathogen among food animals. Despite the threat to public health by T. gondii infections, there's limited understanding of its seroprevalence and trends in food animals across mainland China. This study aimed to estimate the seroprevalence of T. gondii infections among swine, sheep, goats, chickens, and cattle in mainland China from 2010 to 2023.Methods: We searched cross-sectional studies published between 2010 and 2023 that reported the prevalence of T. gondii in food animals from databases including PubMed, Embase, Web of Science, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang data, and the China Science and Technology Journal Database (CQVIP). We performed subgroup analyses to explore the impact of different factors on the seroprevalence of T. gondii. Pooled estimates of T. gondii seroprevalence were calculated with a random-effects model.
    Results: An analysis of 184 studies involving 211985 animals revealed a T. gondii overall seroprevalence of 15.3% (95% CI: 13.1-17.8). Although the seroprevalence of food animals across mainland China was relatively stable from 2010 to 2023, notable variations were observed across different animal types and regions (P < 0.01), along with changes in geographical distribution. Sample type, detection method, animal age, and history of abortion were identified as key risk factors for T. gondii seroprevalence.
    Conclusion: The study conducted a meta-analysis on the seroprevalence of T. gondii in mainland China's Food Animals from 2010 to 2023, and identified key risk factors. These findings advance our understanding of T. gondii infection dynamics, offering critical insights for developing control strategies and guiding public health policies.
    Keywords:  Toxoplasma gondii; epidemiology; meta-analysis; parasitology; public health
    DOI:  https://doi.org/10.3389/fcimb.2024.1381537
  7. Sci Adv. 2024 Apr 19. 10(16): eadm8815
    Mitochondrial energy state controls AMPK-mediated foraging behavior in C. elegans.
    Anežka Vodičková, Annika Müller-Eigner, Chidozie N Okoye, Andrew P Bischer, Jacob Horn, Shon A Koren, Nada Ahmed Selim, Andrew P Wojtovich.
      Organisms surveil and respond to their environment using behaviors entrained by metabolic cues that reflect food availability. Mitochondria act as metabolic hubs and at the center of mitochondrial energy production is the protonmotive force (PMF), an electrochemical gradient generated by metabolite consumption. The PMF serves as a central integrator of mitochondrial status, but its role in governing metabolic signaling is poorly understood. We used optogenetics to dissipate the PMF in Caenorhabditis elegans tissues to test its role in food-related behaviors. Our data demonstrate that PMF reduction in the intestine is sufficient to initiate locomotor responses to acute food deprivation. This behavioral adaptation requires the cellular energy regulator AMP-activated protein kinase (AMPK) in neurons, not in the intestine, and relies on mitochondrial dynamics and axonal trafficking. Our results highlight a role for intestinal PMF as an internal metabolic cue, and we identify a bottom-up signaling axis through which changes in the PMF trigger AMPK activity in neurons to promote foraging behavior.
    DOI:  https://doi.org/10.1126/sciadv.adm8815
  8. Oncogene. 2024 Apr 17.
    ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and regulates the Warburg effect in breast cancer.
    Zibin Zhou, Xiyuan Zheng, Jianxin Zhao, Aiyun Yuan, Zhuan Lv, Guangcan Shao, Bin Peng, Meng-Qiu Dong, Quan Xu, Xingzhi Xu, Jing Li.
      Pyruvate kinase M2 (PKM2) is a central metabolic enzyme driving the Warburg effect in tumor growth. Previous investigations have demonstrated that PKM2 is subject to O-linked β-N-acetylglucosamine (O-GlcNAc) modification, which is a nutrient-sensitive post-translational modification. Here we found that unc-51 like autophagy activating kinase 1 (ULK1), a glucose-sensitive kinase, interacts with PKM2 and phosphorylates PKM2 at Ser333. Ser333 phosphorylation antagonizes PKM2 O-GlcNAcylation, promotes its tetramer formation and enzymatic activity, and decreases its nuclear localization. As PKM2 is known to have a nuclear role in regulating c-Myc, we also show that PKM2-S333 phosphorylation inhibits c-Myc expression. By downregulating glucose consumption and lactate production, PKM2 pS333 attenuates the Warburg effect. Through mouse xenograft assays, we demonstrate that the phospho-deficient PKM2-S333A mutant promotes tumor growth in vivo. In conclusion, we identified a ULK1-PKM2-c-Myc axis in inhibiting breast cancer, and a glucose-sensitive phosphorylation of PKM2 in modulating the Warburg effect.
    DOI:  https://doi.org/10.1038/s41388-024-03035-y
  9. FEBS Lett. 2024 Apr 16.
    Molecular dynamics simulations of intracellular lipid droplets: a new tool in the toolbox.
    Jennifer Sapia, Stefano Vanni.
      Lipid droplets (LDs) are ubiquitous intracellular organelles with a central role in multiple lipid metabolic pathways. However, identifying correlations between their structural properties and their biological activity has proved challenging, owing to their unique physicochemical properties as compared with other cellular membranes. In recent years, molecular dynamics (MD) simulations, a computational methodology allowing the accurate description of molecular assemblies down to their individual components, have been demonstrated to be a useful and powerful approach for studying LD structural and dynamical properties. In this short review, we attempt to highlight, as comprehensively as possible, how MD simulations have contributed to our current understanding of multiple molecular mechanisms involved in LD biology.
    Keywords:  computational biochemistry; fat storage; lipid droplets; membrane biology; molecular dynamics
    DOI:  https://doi.org/10.1002/1873-3468.14879
  10. BMC Infect Dis. 2024 Apr 16. 24(1): 408
    Effect of concurrent infection of Helicobacter pylori with Toxoplasma gondii infection on gastric pathology.
    Marwa A Gouda, Sara A Saied, Ahmed Edrees, Rasha Galal Mostafa, Ashraf Elfert, Aya Abdallah Seleem, Asmaa Shams, Sameh Afify.
      BACKGROUND: Toxoplasma gondii (T. gondii) and Helicobacter pylori (H. pylori) are among the most prevalent foodborne parasitic and bacterial infections worldwide. However, the concurrent impact of coinfection on gastric pathology has yet to be studied in depth. The effect of coinfection generally either adds a synergetic or antagonistic impact; we aimed in the current work to assess the impact of T. gondii coinfection on the progression of H. pylori-associated gastric pathology and reporting H. pylori virulent strains. The study was conducted on 82 patients complaining of persistent gastrointestinal symptoms with failed treatment response and prone to endoscopy. They were subjected to stool examination to detect H. pylori antigen, serological screening for latent toxoplasmosis, endoscopy, histopathological examination, and molecular detection of H. pylori virulence strains in gastric biopsies. Out of the 82 patients, 62 patients were positive for H. pylori antigen in stool and 55 patients confirmed positivity by histopathology; out of them, 37 patients had isolated Vac As1 variants, 11 patients had combined Vac As1 and Cag A variants, and 7 patients had combined Vac As1, Cag A and VacAs2 variants. Patients with the combined two or three variances showed significantly deteriorated histopathological features than patients with a single Vac As1 variant (P < 0.05). Latent toxoplasmosis was positive among 35/82 patients. Combined H. pylori and Toxoplasma gondii infection had significantly marked inflammation than patients with isolated infection (P < 0.05).CONCLUSION: Screening for toxoplasmosis among H. pylori-infected patients is recommended as it is considered a potential risk factor for gastric inflammation severity. H. pylori gastric inflammation may be heightened by Toxoplasma coinfection.
    Keywords:   Cag A ; Helicobacter pylori ; Toxoplasma ; Vac As1 ; Histopathological features; Humans
    DOI:  https://doi.org/10.1186/s12879-024-09270-8
  11. Epigenomics. 2024 Apr 19.
    Current trends in clinical trials and the development of small molecule epigenetic inhibitors as cancer therapeutics.
    Nazanin Zohourian, James Al Brown.
      Epigenetic mechanisms control and regulate normal chromatin structure and gene expression patterns, with epigenetic dysregulation observed in many different cancer types. Importantly, epigenetic modifications are reversible, offering the potential to silence oncogenes and reactivate tumor suppressors. Small molecule drugs manipulating these epigenetic mechanisms are at the leading edge of new therapeutic options for cancer treatment. The clinical use of histone deacetyltransferases inhibitors (HDACi) demonstrates the effectiveness of targeting epigenetic mechanisms for cancer treatment. Notably, the development of new classes of inhibitors, including lysine acetyltransferase inhibitors (KATi), are the future of epigenetic-based therapeutics. We outline the progress of current classes of small molecule epigenetic drugs for use against cancer (preclinical and clinical) and highlight the potential market growth in epigenetic-based therapeutics.
    Keywords:  HAT; KAT; acetyltransferase; cancer; epigenetic; inhibitor; lysine; precision; small molecule; targeted; therapeutic
    DOI:  https://doi.org/10.2217/epi-2023-0443
  12. Life Sci. 2024 Apr 13. pii: S0024-3205(24)00229-7. [Epub ahead of print]346 122639
    Deciphering the interplay of histone post-translational modifications in cancer: Co-targeting histone modulators for precision therapy.
    Rawan R Kawaf, Wafaa S Ramadan, Raafat El-Awady.
      Chromatin undergoes dynamic regulation through reversible histone post-translational modifications (PTMs), orchestrated by "writers," "erasers," and "readers" enzymes. Dysregulation of these histone modulators is well implicated in shaping the cancer epigenome and providing avenues for precision therapies. The approval of six drugs for cancer therapy targeting histone modulators, along with the ongoing clinical trials of numerous candidates, represents a significant advancement in the field of precision medicine. Recently, it became apparent that histone PTMs act together in a coordinated manner to control gene expression. The intricate crosstalk of histone PTMs has been reported to be dysregulated in cancer, thus emerging as a critical factor in the complex landscape of cancer development. This formed the foundation of the swift emergence of co-targeting different histone modulators as a new strategy in cancer therapy. This review dissects how histone PTMs, encompassing acetylation, phosphorylation, methylation, SUMOylation and ubiquitination, collaboratively influence the chromatin states and impact cellular processes. Furthermore, we explore the significance of histone modification crosstalk in cancer and discuss the potential of targeting histone modification crosstalk in cancer management. Moreover, we underscore the significant strides made in developing dual epigenetic inhibitors, which hold promise as emerging candidates for effective cancer therapy.
    Keywords:  Epigenetic drugs; Epigenetics; Histone modification crosstalk; Histone post-translational modifications; cancer therapy
    DOI:  https://doi.org/10.1016/j.lfs.2024.122639
  13. Nat Commun. 2024 Apr 16. 15(1): 3267
    ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA.
    Xinlei Wei, Xue Yang, Congcong Hu, Qiangzi Li, Qianqian Liu, Yue Wu, Leipeng Xie, Xiao Ning, Fei Li, Tao Cai, Zhiguang Zhu, Yi-Heng P Job Zhang, Yanfei Zhang, Xuejun Chen, Chun You.
      In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP+/NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.
    DOI:  https://doi.org/10.1038/s41467-024-46871-y
  14. PLoS One. 2024 ;19(4): e0302374
    Class I histone deacetylases inhibition reverses memory impairment induced by acute stress in mice.
    Heidy Martínez-Pacheco, Rossana Citlali Zepeda, Ofir Picazo, Gina L Quirarte, Gabriel Roldán-Roldán.
      While chronic stress induces learning and memory impairments, acute stress may facilitate or prevent memory consolidation depending on whether it occurs during the learning event or before it, respectively. On the other hand, it has been shown that histone acetylation regulates long-term memory formation. This study aimed to evaluate the effect of two inhibitors of class I histone deacetylases (HDACs), 4-phenylbutyrate (PB) and IN14 (100 mg/kg/day, ip for 2 days), on memory performance in mice exposed to a single 15-min forced swimming stress session. Plasma corticosterone levels were determined 30 minutes after acute swim stress in one group of mice. In another experimental series, independent groups of mice were trained in one of three different memory tasks: Object recognition test, Elevated T maze, and Buried food location test. Subsequently, the hippocampi were removed to perform ELISA assays for histone deacetylase 2 (HDAC2) expression. Acute stress induced an increase in plasma corticosterone levels, as well as hippocampal HDAC2 content, along with an impaired performance in memory tests. Moreover, PB and IN14 treatment prevented memory loss in stressed mice. These findings suggest that HDAC2 is involved in acute stress-induced cognitive impairment. None of the drugs improved memory in non-stressed animals, indicating that HDACs inhibitors are not cognitive boosters, but rather potentially useful drugs for mitigating memory deficits.
    DOI:  https://doi.org/10.1371/journal.pone.0302374
  15. J Zhejiang Univ Sci B. 2024 Apr 07. 1-5
    Energy deprivation-induced autophagy and aggrephagy: insights from yeast and mammals.
    Siyu Fan, Yingcong Chen, Weijing Yao, Cong Yi.
      Autophagy plays a crucial role in maintaining cellular homeostasis in response to various stimuli. Compared to research on nutrient deprivation-induced autophagy, the understanding of the molecular mechanisms and physiological/pathological significance of autophagy triggered by energy deprivation remains limited. A primary focus of our lab is to elucidate how cells sense energy deprivation and initiate autophagy. Using the model organisms Saccharomyces cerevisiae and mammalian cells, we found that cellular reactive oxygen species (ROS), DNA damage sensor Mec1, and mitochondrial aerobic respiration play essential roles in the autophagy induced by energy deprivation. This review aims to provide a concise overview of these research findings.
    Keywords:  Autophagy; Chaperonin-containing TCP-1, subunit 2 (CCT2); Glucose starvation; Solid aggrephagy
    DOI:  https://doi.org/10.1631/jzus.B2300884
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