bims-mecosi Biomed News
on Membrane contact sites
Issue of 2021–11–28
nine papers selected by
Verena Kohler, Stockholm University
  1. Cellular senescence links mitochondria-ER contacts and aging.
  2. The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis.
  3. Connection Lost, MAM: Errors in ER-Mitochondria Connections in Neurodegenerative Diseases.
  4. PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.
  5. PACS-2 attenuates diabetic kidney disease via the enhancement of mitochondria-associated endoplasmic reticulum membrane formation.
  6. Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson's Disease: The Role of Brain Renin Angiotensin System Components.
  7. ER-localized phosphatidylethanolamine synthase plays a conserved role in lipid droplet formation.
  8. ER Morphology in the Pathogenesis of Hereditary Spastic Paraplegia.
  9. ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1.
  1. Commun Biol. 2021 Nov 24. 4(1): 1323
    Cellular senescence links mitochondria-ER contacts and aging.
    Dorian V Ziegler, Nadine Martin, David Bernard.
      Membrane contact sites emerged in the last decade as key players in the integration, regulation and transmission of many signals within cells, with critical impact in multiple pathophysiological contexts. Numerous studies accordingly point to a role for mitochondria-endoplasmic reticulum contacts (MERCs) in modulating aging. Nonetheless, the driving cellular mechanisms behind this role remain unclear. Recent evidence unravelled that MERCs regulate cellular senescence, a state of permanent proliferation arrest associated with a pro-inflammatory secretome, which could mediate MERC impact on aging. Here we discuss this idea in light of recent advances supporting an interplay between MERCs, cellular senescence and aging.
    DOI:  https://doi.org/10.1038/s42003-021-02840-5
  2. J Cell Sci. 2021 Nov 25. pii: jcs.259073. [Epub ahead of print]
    The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis.
    Beichen Xie, Styliani Panagiotou, Jing Cen, Patrick Gilon, Peter Bergsten, Olof Idevall-Hagren.
      Endoplasmic reticulum (ER) - plasma membrane (PM) contacts are sites of lipid exchange and Ca2+ transport, and both lipid transport proteins and Ca2+ channels specifically accumulate at these locations. In pancreatic β-cells, both lipid- and Ca2+ signaling are essential for insulin secretion. The recently characterized lipid transfer protein TMEM24 dynamically localize to ER-PM contact sites and provide phosphatidylinositol, a precursor of PI(4)P and PI(4,5)P2, to the plasma membrane. β-cells lacking TMEM24 exhibit markedly suppressed glucose-induced Ca2+ oscillations and insulin secretion but the underlying mechanism is not known. We now show that TMEM24 only weakly interact with the PM, and dissociates in response to both diacylglycerol and nanomolar elevations of cytosolic Ca2+. Loss of TMEM24 results in hyper-accumulation of Ca2+ in the ER and in excess Ca2+ entry into mitochondria, with resulting impairment in glucose-stimulated ATP production.
    Keywords:  Ca2+; Membrane contact sites; mitochondria
    DOI:  https://doi.org/10.1242/jcs.259073
  3. Brain Sci. 2021 Oct 28. pii: 1437. [Epub ahead of print]11(11):
    Connection Lost, MAM: Errors in ER-Mitochondria Connections in Neurodegenerative Diseases.
    Ashu Johri, Abhishek Chandra.
      Mitochondria associated membranes (MAMs), as the name suggests, are the membranes that physically and biochemically connect mitochondria with endoplasmic reticulum. MAMs not only structurally but also functionally connect these two important organelles within the cell which were previously thought to exist independently. There are multiple points of communication between ER-mitochondria and MAMs play an important role in both ER and mitochondria functions such as Ca2+ homeostasis, proteostasis, mitochondrial bioenergetics, movement, and mitophagy. The number of disease-related proteins and genes being associated with MAMs has been continually on the rise since its discovery. There is an overwhelming overlap between the biochemical functions of MAMs and processes affected in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Thus, MAMs have received well-deserving and much delayed attention as modulators for ER-mitochondria communication and function. This review briefly discusses the recent progress made in this now fast developing field full of promise for very exciting future therapeutic discoveries.
    Keywords:  Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; mitochondria associated membranes (MAMs)
    DOI:  https://doi.org/10.3390/brainsci11111437
  4. J Cell Biol. 2022 Jan 03. pii: e202103141. [Epub ahead of print]221(1):
    PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.
    Asami Kawasaki, Akiko Sakai, Hiroki Nakanishi, Junya Hasegawa, Tomohiko Taguchi, Junko Sasaki, Hiroyuki Arai, Takehiko Sasaki, Michihiro Igarashi, Fubito Nakatsu.
      Membrane contact sites (MCSs) serve as a zone for nonvesicular lipid transport by oxysterol-binding protein (OSBP)-related proteins (ORPs). ORPs mediate lipid countertransport, in which two distinct lipids are transported counterdirectionally. How such lipid countertransport controls specific biological functions, however, remains elusive. We report that lipid countertransport by ORP10 at ER-endosome MCSs regulates retrograde membrane trafficking. ORP10, together with ORP9 and VAP, formed ER-endosome MCSs in a phosphatidylinositol 4-phosphate (PI4P)-dependent manner. ORP10 exhibited a lipid exchange activity toward its ligands, PI4P and phosphatidylserine (PS), between liposomes in vitro, and between the ER and endosomes in situ. Cell biological analysis demonstrated that ORP10 supplies a pool of PS from the ER, in exchange for PI4P, to endosomes where the PS-binding protein EHD1 is recruited to facilitate endosome fission. Our study highlights a novel lipid exchange at ER-endosome MCSs as a nonenzymatic PI4P-to-PS conversion mechanism that organizes membrane remodeling during retrograde membrane trafficking.
    DOI:  https://doi.org/10.1083/jcb.202103141
  5. Cell Death Dis. 2021 Nov 26. 12(12): 1107
    PACS-2 attenuates diabetic kidney disease via the enhancement of mitochondria-associated endoplasmic reticulum membrane formation.
    Mei Xue, Ting Fang, Hongxi Sun, Ying Cheng, Ting Li, Chaofei Xu, Chao Tang, Xiaohuan Liu, Bei Sun, Liming Chen.
      The altered homeostasis of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) was closely associated with the pathological process of nervous system diseases and insulin resistance. Here, the exact implication of phosphofurin acidic cluster sorting protein 2 (PCAS-2), an anchor protein in the MAM interface, in diabetic kidney disease was investigated. In the kidneys of type 1 and type 2 diabetes mice and HG-induced HK-2 cells, a notable disruption of ER-mitochondria interactions, accompanied by a decreased PACS-2 expression in all subcellular fractions. Furthermore, PACS-2 knockout mice with diabetes displayed accelerated development of proteinuria, deterioration of kidney function, and aggravated disruption of MAM area, ER stress, mitochondrial dysfunction, renal apoptosis, and fibrosis. However, overexpression of PACS-2 effectively protected diabetic kidneys and HG-treated HK-2 cells from renal tubular impairments. Importantly, experimental uncoupling of ER-mitochondria contacts reversed the protective effects of PACS-2 restoration on HK-2 cells under HG conditions. In summary, our data indicate a pivotal role of PACS-2 in the development of diabetic renal tubular injury via the stabilization of MAM.
    DOI:  https://doi.org/10.1038/s41419-021-04408-x
  6. Biomolecules. 2021 Nov 10. pii: 1669. [Epub ahead of print]11(11):
    Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson's Disease: The Role of Brain Renin Angiotensin System Components.
    Tuladhar Sunanda, Bipul Ray, Arehally M Mahalakshmi, Abid Bhat, Luay Rashan, Wiramon Rungratanawanich, Byoung-Joon Song, Musthafa Mohamed Essa, Meena Kishore Sakharkar, Saravana Babu Chidambaram.
      The past few decades have seen an increased emphasis on the involvement of the mitochondrial-associated membrane (MAM) in various neurodegenerative diseases, particularly in Parkinson's disease (PD) and Alzheimer's disease (AD). In PD, alterations in mitochondria, endoplasmic reticulum (ER), and MAM functions affect the secretion and metabolism of proteins, causing an imbalance in calcium homeostasis and oxidative stress. These changes lead to alterations in the translocation of the MAM components, such as IP3R, VDAC, and MFN1 and 2, and consequently disrupt calcium homeostasis and cause misfolded proteins with impaired autophagy, distorted mitochondrial dynamics, and cell death. Various reports indicate the detrimental involvement of the brain renin-angiotensin system (RAS) in oxidative stress, neuroinflammation, and apoptosis in various neurodegenerative diseases. In this review, we attempted to update the reports (using various search engines, such as PubMed, SCOPUS, Elsevier, and Springer Nature) demonstrating the pathogenic interactions between the various proteins present in mitochondria, ER, and MAM with respect to Parkinson's disease. We also made an attempt to speculate the possible involvement of RAS and its components, i.e., AT1 and AT2 receptors, angiotensinogen, in this crosstalk and PD pathology. The review also collates and provides updated information on the role of MAM in calcium signaling, oxidative stress, neuroinflammation, and apoptosis in PD.
    Keywords:  ER stress; ER–mitochondria crosstalk; brain renin angiotensin system; mitochondrial dysfunction; mitochondrial-associated membrane (MAM)
    DOI:  https://doi.org/10.3390/biom11111669
  7. Mol Biol Cell. 2021 Nov 24. mbcE21110558T
    ER-localized phosphatidylethanolamine synthase plays a conserved role in lipid droplet formation.
    Mehmet Oguz Gok, Natalie Ortiz Speer, W Mike Henne, Jonathan R Friedman.
      The asymmetric distribution of phospholipids in membranes is a fundamental principle of cellular compartmentalization and organization. Phosphatidylethanolamine (PE), a nonbilayer phospholipid that contributes to organelle shape and function, is synthesized at several subcellular localizations via semi-redundant pathways. Previously, we demonstrated in budding yeast that the PE synthase Psd1, which primarily operates on the mitochondrial inner membrane, is additionally targeted to the ER. While ER-localized Psd1 is required to support cellular growth in the absence of redundant pathways, its physiological function is unclear. We now demonstrate that ER-localized Psd1 sub-localizes on the ER to lipid droplet (LD) attachment sites and show it is specifically required for normal LD formation. We also find that the role of phosphatidylserine decarboxylase (PSD) enzymes in LD formation is conserved in other organisms. Thus, we have identified PSD enzymes as novel regulators of LDs and demonstrate that both mitochondria and LDs in yeast are organized and shaped by the spatial positioning of a single PE synthesis enzyme.
    DOI:  https://doi.org/10.1091/mbc.E21-11-0558-T
  8. Cells. 2021 Oct 25. pii: 2870. [Epub ahead of print]10(11):
    ER Morphology in the Pathogenesis of Hereditary Spastic Paraplegia.
    Sonia Sonda, Diana Pendin, Andrea Daga.
      The endoplasmic reticulum (ER) is the most abundant and widespread organelle in cells. Its peculiar membrane architecture, formed by an intricate network of tubules and cisternae, is critical to its multifaceted function. Regulation of ER morphology is coordinated by a few ER-specific membrane proteins and is thought to be particularly important in neurons, where organized ER membranes are found even in the most distant neurite terminals. Mutation of ER-shaping proteins has been implicated in the neurodegenerative disease hereditary spastic paraplegia (HSP). In this review we discuss the involvement of these proteins in the pathogenesis of HSP, focusing on the experimental evidence linking their molecular function to disease onset. Although the precise biochemical activity of some ER-related HSP proteins has been elucidated, the pathological mechanism underlying ER-linked HSP is still undetermined and needs to be further investigated.
    Keywords:  ER-shaping proteins; endoplasmic reticulum; hereditary spastic paraplegia
    DOI:  https://doi.org/10.3390/cells10112870
  9. Exp Mol Med. 2021 Nov 26.
    ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1.
    Seong Keun Sonn, Seungwoon Seo, Jaemoon Yang, Ki Sook Oh, Hsiuchen Chen, David C Chan, Kunsoo Rhee, Kyung S Lee, Young Yang, Goo Taeg Oh.
      C1q/TNF-related protein 1 (CTRP1) is a CTRP family member that has collagenous and globular C1q-like domains. The secreted form of CTRP1 is known to be associated with cardiovascular and metabolic diseases, but its cellular roles have not yet been elucidated. Here, we showed that cytosolic CTRP1 localizes to the endoplasmic reticulum (ER) membrane and that knockout or depletion of CTRP1 leads to mitochondrial fission defects, as demonstrated by mitochondrial elongation. Mitochondrial fission events are known to occur through an interaction between mitochondria and the ER, but we do not know whether the ER and/or its associated proteins participate directly in the entire mitochondrial fission event. Interestingly, we herein showed that ablation of CTRP1 suppresses the recruitment of DRP1 to mitochondria and provided evidence suggesting that the ER-mitochondrion interaction is required for the proper regulation of mitochondrial morphology. We further report that CTRP1 inactivation-induced mitochondrial fission defects induce apoptotic resistance and neuronal degeneration, which are also associated with ablation of DRP1. These results demonstrate for the first time that cytosolic CTRP1 is an ER transmembrane protein that acts as a key regulator of mitochondrial fission, providing new insight into the etiology of metabolic and neurodegenerative disorders.
    DOI:  https://doi.org/10.1038/s12276-021-00701-z
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:19.