bims-mecosi Biomed News
on Membrane contact sites
Issue of 2024–09–22
nine papers selected by
Verena Kohler, Umeå University
  1. ER-plasma membrane contact sites deliver ER lipids and proteins for rapid cell surface expansion.
  2. A new perspective on liver diseases: Focusing on the mitochondria-associated endoplasmic reticulum membranes.
  3. A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.
  4. Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum.
  5. Systems mapping of bidirectional endosomal transport through the crowded cell.
  6. Endoplasmic reticulum-mitochondria lockdown in Wolfram syndrome.
  7. Organelle landscape analysis using a multiparametric particle-based method.
  8. Correction to "Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions".
  9. The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1.
  1. J Cell Biol. 2024 Dec 02. pii: e202308137. [Epub ahead of print]223(12):
    ER-plasma membrane contact sites deliver ER lipids and proteins for rapid cell surface expansion.
    Madison Smith, Lincoln Gay, Markus Babst.
      As a consequence of hypoosmotic shock, yeast cells swell rapidly and increase the surface area by ∼20% in 20 s. Approximately, 35% of this surface increase is mediated by the ER-plasma membrane contact sites, specifically the tricalbins, which are required for the delivery of both lipids and the GPI-anchored protein Crh2 from the cortical ER to the plasma membrane. Therefore, we propose a new function for the tricalbins: mediating the fusion of the ER to the plasma membrane at contact sites. This proposed fusion is triggered by calcium influx via the stretch-gated channel Cch1 and is supported by the anoctamin Ist2.
    DOI:  https://doi.org/10.1083/jcb.202308137
  2. Pharmacol Res. 2024 Sep 14. pii: S1043-6618(24)00354-2. [Epub ahead of print]208 107409
    A new perspective on liver diseases: Focusing on the mitochondria-associated endoplasmic reticulum membranes.
    Mengyu Guo, Runping Liu, Fukun Zhang, Jiaorong Qu, Yun Yang, Xiaojiaoyang Li.
      The pathogenesis of liver diseases is multifaceted and intricate, posing a persistent global public health challenge with limited therapeutic options. Therefore, further research into liver diseases is imperative for better comprehension and advancement in treatment strategies. Numerous studies have confirmed the endoplasmic reticulum (ER) and mitochondria as key organelles driving liver diseases. Notably, the mitochondrial-associated ER membranes (MAMs) establish a physical and functional connection between the ER and mitochondria, highlighting the importance of inter-organelle communication in maintaining their functional homeostasis. This review delves into the intricate architecture and regulative mechanism of the integrated MAM that facilitate the physiological transfer of signals and substances between organelles. Additionally, we also provide a detailed overview regarding the varied pathogenic roles of malfunctioning MAM in liver diseases, focusing on its involvement in the progression of ER stress and mitochondrial dysfunction, the regulation of mitochondrial dynamics and Ca2+ transfer, as well as the disruption of lipid and glucose homeostasis. Furthermore, the current challenges and prospects associated with MAM in liver disease research are thoroughly discussed. In conclusion, elucidating the specific structure and function of MAM in different liver diseases may pave the way for novel therapeutic strategies.
    Keywords:  Calcium homeostasis; ER stress; Liver diseases; Mitochondria-associated endoplasmic reticulum membranes; Mitochondrial dysfunction
    DOI:  https://doi.org/10.1016/j.phrs.2024.107409
  3. Front Physiol. 2024 ;15 1431030
    A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.
    Xiaolong Chen, Chun Guang Li, Xian Zhou, Minghua Zhu, Jing Jin, Ping Wang.
      Mitochondria and lysosomes play a very important role in maintaining cellular homeostasis, and the dysfunction of these organelles is closely related to many diseases. Recent studies have revealed direct interactions between mitochondria and lysosomes, forming mitochondria-lysosome contact sites that regulate organelle network dynamics and mediate the transport of metabolites between them. Impaired function of these contact sites is not only linked to physiological processes such as glucose and cholesterol transport but also closely related to the pathological processes of metabolic diseases. Here, we highlight the recent progress in understanding the mitochondria-lysosome contact sites, elucidate their role in regulating metabolic homeostasis, and explore the potential implications of this pathway in metabolic disorders.
    Keywords:  cholesterol transport; glucose transport; insulin resistance; mitochondria-lysosome contact sites; nonalcoholic fatty liver disease
    DOI:  https://doi.org/10.3389/fphys.2024.1431030
  4. Nat Cell Biol. 2024 Sep 17.
    Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum.
    Yang Yang, Luis A Valencia, Chih-Hao Lu, Melissa L Nakamoto, Ching-Ting Tsai, Chun Liu, Huaxiao Yang, Wei Zhang, Zeinab Jahed, Wan-Ru Lee, Francesca Santoro, Jen Liou, Joseph C Wu, Bianxiao Cui.
      Contact sites between the endoplasmic reticulum (ER) and plasma membrane (PM) play a crucial role in governing calcium regulation and lipid homeostasis. Despite their significance, the factors regulating their spatial distribution on the PM remain elusive. Inspired by observations in cardiomyocytes, where ER-PM contact sites concentrate on tubular PM invaginations known as transverse tubules, we hypothesize that PM curvature plays a role in ER-PM contact formation. Through precise control of PM invaginations, we show that PM curvatures locally induce the formation of ER-PM contacts in cardiomyocytes. Intriguingly, the junctophilin family of ER-PM tethering proteins, specifically expressed in excitable cells, is the key player in this process, whereas the ubiquitously expressed extended synaptotagmin-2 does not show a preference for PM curvature. At the mechanistic level, we find that the low-complexity region (LCR) and membrane occupation and recognition nexus (MORN) motifs of junctophilins can bind independently to the PM, but both the LCR and MORN motifs are required for targeting PM curvatures. By examining the junctophilin interactome, we identify a family of curvature-sensing proteins-Eps15 homology domain-containing proteins-that interact with the MORN_LCR motifs and facilitate the preferential tethering of junctophilins to curved PM. These findings highlight the pivotal role of PM curvature in the formation of ER-PM contacts in cardiomyocytes and unveil a mechanism for the spatial regulation of ER-PM contacts through PM curvature modulation.
    DOI:  https://doi.org/10.1038/s41556-024-01511-x
  5. Curr Biol. 2024 Sep 09. pii: S0960-9822(24)01138-2. [Epub ahead of print]
    Systems mapping of bidirectional endosomal transport through the crowded cell.
    Marlieke L M Jongsma, Nina Bakker, Lenard M Voortman, Roman I Koning, Erik Bos, Jimmy J L L Akkermans, Lennert Janssen, Jacques Neefjes.
      Kinesin and dynein-dynactin motors move endosomes and other vesicles bidirectionally along microtubules, a process mainly studied under in vitro conditions. Here, we provide a physiological bidirectional transport model following color-coded, endogenously tagged transport-related proteins as they move through a crowded cellular environment. Late endosomes (LEs) surf bidirectionally on Protrudin-enriched endoplasmic reticulum (ER) membrane contact sites, while hopping and gliding along microtubules and bypassing cellular obstacles, such as mitochondria. During bidirectional transport, late endosomes do not switch between opposing Rab7 GTPase effectors, RILP and FYCO1, or their associated dynein and KIF5B motor proteins, respectively. In the endogenous setting, far fewer motors associate with endosomal membranes relative to effectors, implying coordination of transport with other aspects of endosome physiology through GTPase-regulated mechanisms. We find that directionality of transport is provided in part by various microtubule-associated proteins (MAPs), including MID1, EB1, and CEP169, which recruit Lis1-activated dynein motors to microtubule plus ends for transport of early and late endosomal populations. At these microtubule plus ends, activated dynein motors encounter the dynactin subunit p150glued and become competent for endosomal capture and minus-end movement in collaboration with membrane-associated Rab7-RILP. We show that endosomes surf over the ER through the crowded cell and move bidirectionally under the control of MAPs for motor activation and through motor replacement and capture by endosomal anchors.
    Keywords:  FYCO1; Lis1; Protrudin; RILP; Rab7; bidirectional transport; endosomes; membrane contact sites; motor proteins; optogenetics
    DOI:  https://doi.org/10.1016/j.cub.2024.08.026
  6. Cell Calcium. 2024 Sep 12. pii: S0143-4160(24)00113-1. [Epub ahead of print]124 102955
    Endoplasmic reticulum-mitochondria lockdown in Wolfram syndrome.
    Riccardo Filadi, Paola Pizzo.
      Wolfram syndrome (WS) is an incurable autosomal recessive disorder originally described as a mitochondriopathy. In a recent work, Liiv and colleagues found that an impaired endoplasmic reticulum (ER)-to-mitochondria calcium shuttling underlies mitochondrial dysfunction in WS models.
    Keywords:  Calcium signaling; ER-mitochondria contacts; Endoplasmic reticulum; Mitochondria; Wolfram syndrome
    DOI:  https://doi.org/10.1016/j.ceca.2024.102955
  7. PLoS Biol. 2024 Sep;22(9): e3002777
    Organelle landscape analysis using a multiparametric particle-based method.
    Yoshitaka Kurikawa, Ikuko Koyama-Honda, Norito Tamura, Seiichi Koike, Noboru Mizushima.
      Organelles have unique structures and molecular compositions for their functions and have been classified accordingly. However, many organelles are heterogeneous and in the process of maturation and differentiation. Because traditional methods have a limited number of parameters and spatial resolution, they struggle to capture the heterogeneous landscapes of organelles. Here, we present a method for multiparametric particle-based analysis of organelles. After disrupting cells, fluorescence microscopy images of organelle particles labeled with 6 to 8 different organelle markers were obtained, and their multidimensional data were represented in two-dimensional uniform manifold approximation and projection (UMAP) spaces. This method enabled visualization of landscapes of 7 major organelles as well as the transitional states of endocytic organelles directed to the recycling and degradation pathways. Furthermore, endoplasmic reticulum-mitochondria contact sites were detected in these maps. Our proposed method successfully detects a wide array of organelles simultaneously, enabling the analysis of heterogeneous organelle landscapes.
    DOI:  https://doi.org/10.1371/journal.pbio.3002777
  8. Eur J Neurosci. 2024 Sep 20.
    Correction to "Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions".
      
    DOI:  https://doi.org/10.1111/ejn.16544
  9. Proc Natl Acad Sci U S A. 2024 Sep 24. 121(39): e2400531121
    The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1.
    Xiying Wang, Ji Geng, Suman Rimal, Yuxiu Sui, Jie Pan, Zhenghong Qin, Bingwei Lu.
      It is well established that DNA Damage Regulated Autophagy Modulator 1 (DRAM1), a lysosomal protein and a target of p53, participates in autophagy. The cellular functions of DRAM1 beyond autophagy remain elusive. Here, we show p53-dependent upregulation of DRAM1 in mitochondrial damage-induced Parkinson's disease (PD) models and exacerbation of disease phenotypes by DRAM1. We find that the lysosomal location of DRAM1 relies on its intact structure including the cytosol-facing C-terminal domain. Excess DRAM1 disrupts endoplasmic reticulum (ER) structure, triggers ER stress, and induces protective ER-phagy. Mechanistically, DRAM1 interacts with stromal interacting molecule 1 (STIM1) to tether lysosomes to the ER and perturb STIM1 function in maintaining intracellular calcium homeostasis. STIM1 overexpression promotes cellular health by restoring calcium homeostasis, ER stress response, ER-phagy, and AMP-activated protein kinase (AMPK)-Unc-51 like autophagy activating kinase 1 (ULK1) signaling in cells with excess DRAM1. Thus, by promoting organelle contact between lysosomes and the ER, DRAM1 modulates ER structure and function and cell survival under stress. Our results suggest that DRAM1 as a lysosomal protein performs diverse roles in cellular homeostasis and stress response. These findings may have significant implications for our understanding of the role of the p53/DRAM1 axis in human diseases, from cancer to neurodegenerative diseases.
    Keywords:  DRAM1; ER; ER-phagy; calcium homeostasis; lysosome
    DOI:  https://doi.org/10.1073/pnas.2400531121
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