bims-mecosi Biomed News
on Membrane contact sites
Issue of 2023‒07‒30
fourteen papers selected by
Verena Kohler
  1. Increased Phospholipid Flux Bypasses Overlapping Essential Requirements for the Yeast Sac1p Phosphoinositide Phosphatase and ER-PM Membrane Contact Sites.
  2. E-Syt1 Regulates Neuronal Activity-Dependent Endoplasmic Reticulum-Plasma Membrane Junctions and Surface Expression of AMPA Receptors.
  3. COPI-regulated mitochondria-ER contact site formation maintains axonal integrity.
  4. Altered GM1 catabolism affects NMDAR-mediated Ca 2+ signaling at ER-PM junctions and increases synaptic spine formation.
  5. A proximity labeling strategy enables proteomic analysis of inter-organelle membrane contacts.
  6. Yeast Models of Amyotrophic Lateral Sclerosis Type 8 Mimic Phenotypes Seen in Mammalian Cells Expressing Mutant VAPBP56S.
  7. SIRT3 ameliorates diabetes-associated cognitive dysfunction via regulating mitochondria-associated ER membranes.
  8. Molecular Understanding of ER-MT Communication Dysfunction during Neurodegeneration.
  9. Computational Analysis Reveals Unique Binding Patterns of Oxygenated and Deoxygenated Myoglobin to the Outer Mitochondrial Membrane.
  10. Periodicity, mixed-mode oscillations, and multiple timescales in a phosphoinositide-Rho GTPase network.
  11. NPC1-dependent alterations in KV2.1-CaV1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease.
  12. Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP-A.
  13. New Insights on the Uptake and Trafficking of Coenzyme Q.
  14. The ins-and-outs of exosome biogenesis, secretion, and internalization.
  1. J Biol Chem. 2023 Jul 26. pii: S0021-9258(23)02120-8. [Epub ahead of print] 105092
    Increased Phospholipid Flux Bypasses Overlapping Essential Requirements for the Yeast Sac1p Phosphoinositide Phosphatase and ER-PM Membrane Contact Sites.
    Aleksa Nenadic, Mohammad F Zaman, Jesper Johansen, Matthew W Volpiana, Christopher T Beh.
      In budding yeast cells, much of the inner surface of the plasma membrane (PM) is covered with the endoplasmic reticulum (ER). This association is mediated by seven ER membrane proteins that confer cortical ER-PM association at membrane contact sites (MCSs). Several of these membrane "tether" proteins are known to physically interact with the phosphoinositide phosphatase Sac1p. However, it is unclear how or if these interactions are necessary for their interdependent functions. We find that SAC1 inactivation in cells lacking the homologous synaptojanin-like genes INP52 and INP53 results in a significant increase in cortical ER-PM MCSs. We show in sac1Δ, sac1tsinp52Δ inp53Δ, or Δ-super-tether (Δ-s-tether) cells lacking all seven ER-PM tethering genes, that phospholipid biosynthesis is disrupted, and phosphoinositide distribution is altered. Furthermore, SAC1 deletion in Δ-s-tether cells results in lethality, indicating a functional overlap between SAC1 and ER-PM tethering genes. Transcriptomic profiling indicates that SAC1 inactivation in either Δ-s-tether or inp52Δ inp53Δ cells induces an ER membrane stress response and elicits phosphoinositide-dependent changes in expression of autophagy genes. In addition, by isolating high-copy suppressors that rescue sac1Δ Δ-s-tether lethality, we find that key phospholipid biosynthesis genes bypass the overlapping function of SAC1 and ER-PM tethers, and that overexpression of the phosphatidylserine (PS)/phosphatidylinositol-4-phosphate (PI4P) transfer protein Osh6 also provides limited suppression. Combined with lipidomic analysis and determinations of intracellular phospholipid distributions, these results suggest that Sac1p and ER phospholipid flux controls lipid distribution to drive Osh6p-dependent PS/PI4P counter exchange at ER-PM MCSs.
    Keywords:  ER-PM membrane contact sites; Saccharomyces cerevisiae; autophagy; endoplasmic reticulum (ER); phosphatidylinositol phosphate phosphatase; phosphatidylserine; phosphoinositides; phospholipid metabolism; plasma membrane (PM)
    DOI:  https://doi.org/10.1016/j.jbc.2023.105092
  2. Contact (Thousand Oaks). 2023 Jan-Dec;6:6 25152564231185011
    E-Syt1 Regulates Neuronal Activity-Dependent Endoplasmic Reticulum-Plasma Membrane Junctions and Surface Expression of AMPA Receptors.
    Ranran Mao, Chunfang Tong, Jia-Jia Liu.
      Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, and membrane dynamics. However, little is known about the dynamic regulation and functional roles of ER-PM junctions in neurons. Using a split green fluorescent protein-based membrane contact probe, we find that the density of ER-PM contact sites changes dynamically in the dendrites of hippocampal neurons undergoing long-term synaptic potentiation (LTP). We show that the Ca2±-sensing membrane tethering protein Extended Synaptotagmin 1 (E-Syt1) mediates the formation of ER-PM contact sites during LTP. We also show that E-Syt1 is required for neuronal activity-dependent surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors. These findings implicate ER-PM junctions in the regulation of neurotransmitter receptor trafficking and synaptic plasticity.
    Keywords:  AMPAR; E-Syt; calcium; contact; long-term potentiation; synaptic plasticity
    DOI:  https://doi.org/10.1177/25152564231185011
  3. Cell Rep. 2023 Jul 26. pii: S2211-1247(23)00894-X. [Epub ahead of print]42(8): 112883
    COPI-regulated mitochondria-ER contact site formation maintains axonal integrity.
    Daniel C Maddison, Bilal Malik, Leonardo Amadio, Dana M Bis-Brewer, Stephan Züchner, Owen M Peters, Gaynor A Smith.
      Coat protein complex I (COPI) is best known for its role in Golgi-endoplasmic reticulum (ER) trafficking, responsible for the retrograde transport of ER-resident proteins. The ER is crucial to neuronal function, regulating Ca2+ homeostasis and the distribution and function of other organelles such as endosomes, peroxisomes, and mitochondria via functional contact sites. Here we demonstrate that disruption of COPI results in mitochondrial dysfunction in Drosophila axons and human cells. The ER network is also disrupted, and the neurons undergo rapid degeneration. We demonstrate that mitochondria-ER contact sites (MERCS) are decreased in COPI-deficient axons, leading to Ca2+ dysregulation, heightened mitophagy, and a decrease in respiratory capacity. Reintroducing MERCS is sufficient to rescue not only mitochondrial distribution and Ca2+ uptake but also ER morphology, dramatically delaying neurodegeneration. This work demonstrates an important role for COPI-mediated trafficking in MERC formation, which is an essential process for maintaining axonal integrity.
    Keywords:  Axon transport; COPI; CP: Cell biology; Calcium homeostasis; Endoplasmic reticulum; Golgi; Mitochondria; Neuronal cell biology; Vesicle trafficking
    DOI:  https://doi.org/10.1016/j.celrep.2023.112883
  4. bioRxiv. 2023 Jul 11. pii: 2023.07.10.548446. [Epub ahead of print]
    Altered GM1 catabolism affects NMDAR-mediated Ca 2+ signaling at ER-PM junctions and increases synaptic spine formation.
    Jason A Weesner, Ida Annunziata, Diantha van de Vlekkert, Camenzind G Robinson, Yvan Campos, Ashutosh Mishra, Leigh E Fremuth, Elida Gomero, Huimin Hu, Alessandra d'Azzo.
      Endoplasmic reticulum-plasma membrane (ER-PM) junctions mediate Ca 2+ flux across neuronal membranes. The properties of these membrane contact sites are defined by their lipid content, but little attention has been given to glycosphingolipids (GSLs). Here, we show that GM1-ganglioside, an abundant GSL in neuronal membranes, is integral to ER-PM junctions; it interacts with synaptic proteins/receptors and regulates Ca 2+ signaling. In a model of the neurodegenerative lysosomal storage disease, GM1-gangliosidosis, pathogenic accumulation of GM1 at ER-PM junctions due to β-galactosidase deficiency drastically alters neuronal Ca 2+ homeostasis. Mechanistically, we show that GM1 interacts with the phosphorylated NMDAR Ca 2+ channel, thereby increasing Ca 2+ flux, activating ERK signaling, and increasing the number of synaptic spines without increasing synaptic connectivity. Thus, GM1 clustering at ER-PM junctions alters synaptic plasticity and exacerbates the generalized neuronal cell death characteristic of GM1-gangliosidosis.
    DOI:  https://doi.org/10.1101/2023.07.10.548446
  5. iScience. 2023 Jul 21. 26(7): 107159
    A proximity labeling strategy enables proteomic analysis of inter-organelle membrane contacts.
    Maoge Zhou, Bingjie Kong, Xiang Zhang, Ke Xiao, Jing Lu, Weixing Li, Min Li, Zonghong Li, Wei Ji, Junjie Hou, Tao Xu.
      Inter-organelle membrane contacts are highly dynamic and act as central hubs for many biological processes, but the protein compositions remain largely unknown due to the lack of efficient tools. Here, we developed BiFCPL to analyze the contact proteome in living cells by a bimolecular fluorescence complementation (BiFC)-based proximity labeling (PL) strategy. BiFCPL was applied to study mitochondria-endoplasmic reticulum contacts (MERCs) and mitochondria-lipid droplet (LD) contacts. We identified 403 highly confident MERC proteins, including many transiently resident proteins and potential tethers. Moreover, we demonstrated that mitochondria-LD contacts are sensitive to nutrient status. A comparative proteomic analysis revealed that 60 proteins are up- or downregulated at contact sites under metabolic challenge. We verified that SQLE, an enzyme for cholesterol synthesis, accumulates at mitochondria-LD contact sites probably to utilize local ATP for cholesterol synthesis. This work provides an efficient method to identify key proteins at inter-organelle membrane contacts in living cells.
    Keywords:  Biophysics; Membranes; Proteomics
    DOI:  https://doi.org/10.1016/j.isci.2023.107159
  6. Biomolecules. 2023 Jul 19. pii: 1147. [Epub ahead of print]13(7):
    Yeast Models of Amyotrophic Lateral Sclerosis Type 8 Mimic Phenotypes Seen in Mammalian Cells Expressing Mutant VAPBP56S.
    AnnaMari L Stump, Daniel J Rioux, Richard Albright, Guiliano L Melki, Derek C Prosser.
      Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that results in the loss of motor neurons and can occur sporadically or due to genetic mutations. Among the 30 genes linked to familial ALS, a P56S mutation in VAPB, an ER-resident protein that functions at membrane contact sites, causes ALS type 8. Mammalian cells expressing VAPBP56S have distinctive phenotypes, including ER collapse, protein and/or membrane-containing inclusions, and sensitivity to ER stress. VAPB is conserved through evolution and has two homologs in budding yeast, SCS2 and SCS22. Previously, a humanized version of SCS2 bearing disease-linked mutations was described, and it caused Scs2-containing inclusions when overexpressed in yeast. Here, we describe a yeast model for ALS8 in which the two SCS genes are deleted and replaced with a single chromosomal copy of either wild-type or mutant yeast SCS2 or human VAPB expressed from the SCS2 promoter. These cells display ER collapse, the formation of inclusion-like structures, and sensitivity to tunicamycin, an ER stress-inducing drug. Based on the phenotypic similarity to mammalian cells expressing VAPBP56S, we propose that these models can be used to study the molecular basis of cell death or dysfunction in ALS8. Moreover, other conserved ALS-linked genes may create opportunities for the generation of yeast models of disease.
    Keywords:  ALS; ALS8; Saccharomyces cerevisiae; VAPB; amyotrophic lateral sclerosis; endoplasmic reticulum; membrane contact site; neurodegeneration; yeast
    DOI:  https://doi.org/10.3390/biom13071147
  7. J Transl Med. 2023 07 22. 21(1): 494
    SIRT3 ameliorates diabetes-associated cognitive dysfunction via regulating mitochondria-associated ER membranes.
    Yanmin Chang, Cailin Wang, Jiahui Zhu, Siyi Zheng, Shangqi Sun, Yanqing Wu, Xingjun Jiang, Lulu Li, Rong Ma, Gang Li.
      BACKGROUND: Diabetes is associated with an increased risk of cognitive decline and dementia. These diseases are linked with mitochondrial dysfunction, most likely as a consequence of excessive formation of mitochondria-associated membranes (MAMs). Sirtuin3 (SIRT3), a key mitochondrial NAD+-dependent deacetylase, is critical responsible for mitochondrial functional homeostasis and is highly associated with neuropathology. However, the role of SIRT3 in regulating MAM coupling remains unknown.METHODS: Streptozotocin-injected diabetic mice and high glucose-treated SH-SY5Y cells were established as the animal and cellular models, respectively. SIRT3 expression was up-regulated in vivo using an adeno-associated virus in mouse hippocampus and in vitro using a recombinant lentivirus vector. Cognitive function was evaluated using behavioural tests. Hippocampus injury was assessed using Golgi and Nissl staining. Apoptosis was analysed using western blotting and TUNEL assay. Mitochondrial function was detected using flow cytometry and confocal fluorescence microscopy. The mechanisms were investigated using co-immunoprecipitation of VDAC1-GRP75-IP3R complex, fluorescence imaging of ER and mitochondrial co-localisation and transmission electron microscopy of structural analysis of MAMs.
    RESULTS: Our results demonstrated that SIRT3 expression was significantly reduced in high glucose-treated SH-SY5Y cells and hippocampal tissues from diabetic mice. Further, up-regulating SIRT3 alleviated hippocampus injuries and cognitive impairment in diabetic mice and mitigated mitochondrial Ca2+ overload-induced mitochondrial dysfunction and apoptosis. Mechanistically, MAM formation was enhanced under high glucose conditions, which was reversed by genetic up-regulation of SIRT3 via reduced interaction of the VDAC1-GRP75-IP3R complex in vitro and in vivo. Furthermore, we investigated the therapeutic effects of pharmacological activation of SIRT3 in diabetic mice via honokiol treatment, which exhibited similar effects to our genetic interventions.
    CONCLUSIONS: In summary, our findings suggest that SIRT3 ameliorates cognitive impairment in diabetic mice by limiting aberrant MAM formation. Furthermore, targeting the activation of SIRT3 by honokiol provides a promising therapeutic candidate for diabetes-associated cognitive dysfunction. Overall, our study suggests a novel role of SIRT3 in regulating MAM coupling and indicates that SIRT3-targeted therapies are promising for diabetic dementia patients.
    Keywords:  Diabetes-associated cognitive dysfunction; Honokiol; Mitochondria-associated ER membranes; Sirtuin3; VDAC1–GRP75–IP3R complex
    DOI:  https://doi.org/10.1186/s12967-023-04246-9
  8. Mitochondrion. 2023 Jul 24. pii: S1567-7249(23)00068-5. [Epub ahead of print]
    Molecular Understanding of ER-MT Communication Dysfunction during Neurodegeneration.
    Shivkumar S Sammeta, Trupti A Banarase, Sandip R Rahangdale, Nitu L Wankhede, Manish M Aglawe, Brijesh G Taksande, Shubhada V Mangrulkar, Aman B Upaganlawar, Sushruta Koppula, Spandana Rajendra Kopalli, Milind J Umekar, Mayur B Kale.
      Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca2+ homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.
    Keywords:  Alzheimer’s disease; Amyotrophic lateral sclerosis; Mitochondria–ER contact sites (MERCS); Parkinson’s disease; mitochondria–ER-associated membrane (MAM); neurodegeneration
    DOI:  https://doi.org/10.1016/j.mito.2023.07.005
  9. Biomolecules. 2023 Jul 17. pii: 1138. [Epub ahead of print]13(7):
    Computational Analysis Reveals Unique Binding Patterns of Oxygenated and Deoxygenated Myoglobin to the Outer Mitochondrial Membrane.
    Andriy Anishkin, Kiran Kumar Adepu, Dipendra Bhandari, Sean H Adams, Sree V Chintapalli.
      Myoglobin (Mb) interaction with the outer mitochondrial membrane (OMM) promotes oxygen (O2) release. However, comprehensive molecular details on specific contact regions of the OMM with oxygenated (oxy-) and deoxygenated (deoxy-)Mb are missing. We used molecular dynamics (MD) simulations to explore the interaction of oxy- and deoxy-Mb with the membrane lipids of the OMM in two lipid compositions: (a) a typical whole membrane on average, and (b) specifically the cardiolipin-enriched cristae region (contact site). Unrestrained relaxations showed that on average, both the oxy- and deoxy-Mb established more stable contacts with the lipids typical of the cristae contact site, then with those of the average OMM. However, in steered detachment simulations, deoxy-Mb clung more tightly to the average OMM, and oxy-Mb strongly preferred the contact sites of the OMM. The MD simulation analysis further indicated that a non-specific binding, mediated by local electrostatic interactions, existed between charged or polar groups of Mb and the membrane, for stable interaction. To the best of our knowledge, this is the first computational study providing the molecular details of the direct Mb-mitochondria interaction that assisted in distinguishing the preferred localization of oxy- and deoxy-Mb on the OMM. Our findings support the existing experimental evidence on Mb-mitochondrial association and shed more insights on Mb-mediated O2 transport for cellular bioenergetics.
    Keywords:  diffusion; mitochondria; myoglobin
    DOI:  https://doi.org/10.3390/biom13071138
  10. Cell Rep. 2023 Jul 25. pii: S2211-1247(23)00868-9. [Epub ahead of print]42(8): 112857
    Periodicity, mixed-mode oscillations, and multiple timescales in a phosphoinositide-Rho GTPase network.
    Chee San Tong, X J Xǔ, Min Wu.
      While rhythmic contractile behavior is commonly observed at the cellular cortex, the primary focus has been on excitable or periodic events described by simple activator-delayed inhibitor mechanisms. We show that Rho GTPase activation in nocodazole-treated mitotic cells exhibits both simple oscillations and complex mixed-mode oscillations. Rho oscillations with a 20- to 30-s period are regulated by phosphatidylinositol (3,4,5)-trisphosphate (PIP3) via an activator-delayed inhibitor mechanism, while a slow reaction with period of minutes is regulated by phosphatidylinositol 4-kinase via an activator-substrate depletion mechanism. Conversion from simple to complex oscillations can be induced by modulating PIP3 metabolism or altering membrane contact site protein E-Syt1. PTEN depletion results in a period-doubling intermediate, which, like mixed-mode oscillations, is an intermediate state toward chaos. In sum, this system operates at the edge of chaos. Small changes in phosphoinositide metabolism can confer cells with the flexibility to rapidly enter ordered states with different periodicities.
    Keywords:  CP: Cell biology; contractility; membrane contact sites; mitosis; mixed-mode oscillation; phosphoinositides
    DOI:  https://doi.org/10.1016/j.celrep.2023.112857
  11. Nat Commun. 2023 Jul 28. 14(1): 4553
    NPC1-dependent alterations in KV2.1-CaV1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease.
    Maria Casas, Karl D Murray, Keiko Hino, Nicholas C Vierra, Sergi Simó, James S Trimmer, Rose E Dixon, Eamonn J Dickson.
      Lysosomes communicate through cholesterol transfer at endoplasmic reticulum (ER) contact sites. At these sites, the Niemann Pick C1 cholesterol transporter (NPC1) facilitates the removal of cholesterol from lysosomes, which is then transferred to the ER for distribution to other cell membranes. Mutations in NPC1 result in cholesterol buildup within lysosomes, leading to Niemann-Pick Type C (NPC) disease, a progressive and fatal neurodegenerative disorder. The molecular mechanisms connecting NPC1 loss to NPC-associated neuropathology remain unknown. Here we show both in vitro and in an animal model of NPC disease that the loss of NPC1 function alters the distribution and activity of voltage-gated calcium channels (CaV). Underlying alterations in calcium channel localization and function are KV2.1 channels whose interactions drive calcium channel clustering to enhance calcium entry and fuel neurotoxic elevations in mitochondrial calcium. Targeted disruption of KV2-CaV interactions rescues aberrant CaV1.2 clustering, elevated mitochondrial calcium, and neurotoxicity in vitro. Our findings provide evidence that NPC is a nanostructural ion channel clustering disease, characterized by altered distribution and activity of ion channels at membrane contacts, which contribute to neurodegeneration.
    DOI:  https://doi.org/10.1038/s41467-023-39937-w
  12. bioRxiv. 2023 Jul 19. pii: 2023.07.18.549588. [Epub ahead of print]
    Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP-A.
    Bahnisikha Barman, Marisol Ramirez, T Renee Dawson, Qi Liu, Alissa M Weaver.
      Extracellular vesicles (EVs) influence cell phenotypes and functions via protein, nucleic acid and lipid cargoes. EVs are heterogeneous, due to diverse biogenesis mechanisms that remain poorly understood. Our previous study revealed that the endoplasmic rectiulum (ER) membrane contact site (MCS) linker protein VAP-A drives biogenesis of a subset of RNA-enriched EVs. Here, we examine the protein content of VAP-A-regulated EVs. Using label-free proteomics, we identified down- and up-regulated proteins in sEVs purified from VAP-A knockdown (KD) colon cancer cells. Gene set enrichment analysis (GSEA) of the data revealed protein classes that are differentially sorted to SEVs dependent on VAP-A. STRING protein-protein interaction network analysis of the RNA-binding protein (RBP) gene set identified several RNA functional machineries that are downregulated in VAP-A KD EVs, including ribosome, spliceosome, mRNA surveillance, and RNA transport proteins. We also observed downregulation of other functionally interacting protein networks, including cadherin-binding, unfolded protein binding, and ATP-dependent proteins.Significance of the study: Little is known about biogenesis mechanisms that underlie EV heterogeneity. This study explores the protein repertoire of a specific subset of EVs that we recently identified to be generated at ER MCS and that are highly enriched in RNAs. We find that proteins from several classes of RNA machineries, including spliceosomes, are downregulated in EVs purified from cells knocked down for the ER MCS linker protein VAP-A. These data suggest that dynamic regulation of these protein machineries at ER MCS are involved in the sorting of RNA-RBP complexes into EVs.
    DOI:  https://doi.org/10.1101/2023.07.18.549588
  13. Antioxidants (Basel). 2023 Jul 06. pii: 1391. [Epub ahead of print]12(7):
    New Insights on the Uptake and Trafficking of Coenzyme Q.
    Michael D Guile, Akash Jain, Kyle A Anderson, Catherine F Clarke.
      Coenzyme Q (CoQ) is an essential lipid with many cellular functions, such as electron transport for cellular respiration, antioxidant protection, redox homeostasis, and ferroptosis suppression. Deficiencies in CoQ due to aging, genetic disease, or medication can be ameliorated by high-dose supplementation. As such, an understanding of the uptake and transport of CoQ may inform methods of clinical use and identify how to better treat deficiency. Here, we review what is known about the cellular uptake and intracellular distribution of CoQ from yeast, mammalian cell culture, and rodent models, as well as its absorption at the organism level. We discuss the use of these model organisms to probe the mechanisms of uptake and distribution. The literature indicates that CoQ uptake and distribution are multifaceted processes likely to have redundancies in its transport, utilizing the endomembrane system and newly identified proteins that function as lipid transporters. Impairment of the trafficking of either endogenous or exogenous CoQ exerts profound effects on metabolism and stress response. This review also highlights significant gaps in our knowledge of how CoQ is distributed within the cell and suggests future directions of research to better understand this process.
    Keywords:  coenzyme Q; lipid trafficking; membrane contact sites; mitochondria transport; ubiquinone
    DOI:  https://doi.org/10.3390/antiox12071391
  14. Trends Cell Biol. 2023 Jul 26. pii: S0962-8924(23)00129-0. [Epub ahead of print]
    The ins-and-outs of exosome biogenesis, secretion, and internalization.
    Subhash B Arya, Samuel P Collie, Carole A Parent.
      Exosomes are specialized cargo delivery vesicles secreted from cells by fusion of multivesicular bodies (MVBs) with the plasma membrane (PM). While the function of exosomes during physiological and pathological events has been extensively reported, there remains a lack of understanding of the mechanisms that regulate exosome biogenesis, secretion, and internalization. Recent technological and methodological advances now provide details about MVB/exosome structure as well as the pathways of exosome biogenesis, secretion, and uptake. In this review, we outline our current understanding of these processes and highlight outstanding questions following on recent discoveries in the field.
    Keywords:  ER–endosome membrane contact sites; cargo sorting; cholesterol; exosomes; multivesicular bodies
    DOI:  https://doi.org/10.1016/j.tcb.2023.06.006
This page is being maintained by Thomas Krichel. It was last updated on 2023‒10‒30 at 8:22.