bims-mecosi Biomed News
on Membrane contact sites
Issue of 2022‒07‒24
seven papers selected by
Verena Kohler
  1. Finding new friends and revisiting old ones - How plant lipid droplets connect with other subcellular structures.
  2. Balancing energy and protein homeostasis at ER-mitochondria contact sites.
  3. LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides.
  4. In situ architecture of the lipid transport protein VPS13C at ER-lysosome membrane contacts.
  5. Effects of Curcumin on Mitochondrial Function, Endoplasmic Reticulum Stress, and Mitochondria-Associated Endoplasmic Reticulum Membranes in the Jejunum of Oxidative Stress Piglets.
  6. Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11.
  7. The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity.
  1. New Phytol. 2022 Jul 18.
    Finding new friends and revisiting old ones - How plant lipid droplets connect with other subcellular structures.
    Patricia Scholz, Kent D Chapman, Robert T Mullen, Till Ischebeck.
      The number of described contact sites between different subcellular compartments and structures in eukaryotic cells has increased dramatically in recent years and, as such, has substantially reinforced the well-known premise that these kinds of connections are essential for overall cellular organization and the proper functioning of cellular metabolic and signaling pathways. Here, we discuss contact sites involving plant lipid droplets (LDs), including LD-endoplasmic reticulum (ER) connections that mediate the biogenesis of new LDs at the ER, LD-peroxisome connections, that facilitate the degradation of LD-stored triacylglycerols (TAGs), and the more recently discovered LD-plasma membrane connections, which involve at least three novel proteins, but have a yet unknown physiological function(s).
    Keywords:  ER; Lipid droplet; membrane contact sites; oleosome; peroxisome; plasma membrane
    DOI:  https://doi.org/10.1111/nph.18390
  2. Sci Signal. 2022 Jul 05. 15(741): eabm7524
    Balancing energy and protein homeostasis at ER-mitochondria contact sites.
    Amado Carreras-Sureda, Guido Kroemer, Julio Cesar Cardenas, Claudio Hetz.
      The endoplasmic reticulum (ER) is the largest organelle of the cell and participates in multiple essential functions, including the production of secretory proteins, lipid synthesis, and calcium storage. Sustaining proteostasis requires an intimate coupling with energy production. Mitochondrial respiration evolved to be functionally connected to ER physiology through a physical interface between both organelles known as mitochondria-associated membranes. This quasi-synaptic structure acts as a signaling hub that tunes the function of both organelles in a bidirectional manner and controls proteostasis, cell death pathways, and mitochondrial bioenergetics. Here, we discuss the main signaling mechanisms governing interorganellar communication and their putative role in diseases including cancer and neurodegeneration.
    DOI:  https://doi.org/10.1126/scisignal.abm7524
  3. Cell Calcium. 2022 Jul 11. pii: S0143-4160(22)00104-X. [Epub ahead of print]106 102631
    LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides.
    Gergo Gulyas, Marek K Korzeniowski, Carlos Ernesto Bastián Eugenio, Luis Vaca, Yeun Ju Kim, Tamas Balla.
      The ER-resident proteins STIM1 together with the plasma membrane (PM)-localized Orai1 channels constitute the molecular components of the store-operated Ca2+ entry (SOCE) pathway. Prepositioning of STIM1 to the peripheral ER close to the PM ensures its efficient interaction with Orai1 upon a decrease in the ER luminal Ca2+ concentration. The C-terminal polybasic domain of STIM1 has been identified as mediating the interaction with PM phosphoinositides and hence positions the molecule to ER-PM contact sites. Here we show that STIM1 requires PM phosphatidylinositol 4-phosphate (PI4P) for efficient PM interaction. Accordingly, oxysterol binding protein related proteins (ORPs) that work at ER-PM junctions and consume PI4P gradients exert important control over the Ca2+ entry process. These studies reveal an important connection between non-vesicular lipid transport at ER-PM contact sites and regulation of ER Ca2+store refilling.
    Keywords:  Calcium; ER; Lipid transfer proteins; Membrane contact sites; Phosphatidylinositol; Phosphoinositides; Plasma membrane
    DOI:  https://doi.org/10.1016/j.ceca.2022.102631
  4. Proc Natl Acad Sci U S A. 2022 Jul 19. 119(29): e2203769119
    In situ architecture of the lipid transport protein VPS13C at ER-lysosome membrane contacts.
    Shujun Cai, Yumei Wu, Andrés Guillén-Samander, William Hancock-Cerutti, Jun Liu, Pietro De Camilli.
      VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by a bridge-like mechanism. Direct evidence for this hypothesis from a full-length structure and from electron microscopy (EM) studies in situ is still missing, however. Here, we have capitalized on AlphaFold predictions to complement the structural information already available about VPS13 and to generate a full-length model of human VPS13C, the Parkinson's disease-linked VPS13 paralog localized at contacts between the endoplasmic reticulum (ER) and endo/lysosomes. Such a model predicts an ∼30-nm rod with a hydrophobic groove that extends throughout its length. We further investigated whether such a structure can be observed in situ at ER-endo/lysosome contacts. To this aim, we combined genetic approaches with cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) to examine HeLa cells overexpressing this protein (either full length or with an internal truncation) along with VAP, its anchoring binding partner at the ER. Using these methods, we identified rod-like densities that span the space separating the two adjacent membranes and that match the predicted structures of either full-length VPS13C or its shorter truncated mutant, thus providing in situ evidence for a bridge model of VPS13 in lipid transport.
    Keywords:  VPS13; cryo-electron tomography; lipid-transfer protein; membrane contact sites
    DOI:  https://doi.org/10.1073/pnas.2203769119
  5. J Agric Food Chem. 2022 Jul 18.
    Effects of Curcumin on Mitochondrial Function, Endoplasmic Reticulum Stress, and Mitochondria-Associated Endoplasmic Reticulum Membranes in the Jejunum of Oxidative Stress Piglets.
    Xin Li, Jiang Zhu, Qian Lin, Minjie Yu, Jianjun Lu, Jie Feng, Caihong Hu.
      Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are not only critical for the communication between two organelles but also crucial for cellular processes such as energy metabolism, calcium signaling, and mitochondrial dynamics. The effects of curcumin on jejunal mitochondria, ER, and MAMs in piglets under diquat-induced oxidative stress were assessed. Twenty-four piglets (35 days old, weaned at 21 days, 9.54 ± 0.28 kg, six piglets per group) were used in the study: (1) control group; (2) control + curcumin group; (3) diquat group; and (4) diquat + curcumin group. Curcumin was mixed with the basic diet at 200 mg/kg and fed to piglets. Piglets were administered intraperitoneally of 0.9% saline solution or diquat at 10 mg/kg body weight on the first day. Compared with the diquat group, curcumin improved jejunal morphology and barrier function. Meanwhile, curcumin improved mitochondrial function and ultrastructure, alleviated endoplasmic reticulum stress (ERS), and inhibited apoptosis induced by diquat. Moreover, curcumin prevented excessive MAM formation and alleviated MAM disorder. In conclusion, dietary curcumin ameliorated jejunal damage and mitochondrial dysfunction, attenuated ERS, and alleviated MAM disorder in oxidative stress piglets induced by diquat.
    Keywords:  MAMs; curcumin; endoplasmic reticulum; intestinal injury; mitochondria; oxidative stress; piglets
    DOI:  https://doi.org/10.1021/acs.jafc.2c02824
  6. Redox Biol. 2022 Jul 16. pii: S2213-2317(22)00182-3. [Epub ahead of print]55 102410
    Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11.
    Ilaria Sorrentino, Mauro Galli, Iria Medraño-Fernandez, Roberto Sitia.
      Some aquaporins (AQPs) can transport H2O2 across membranes, allowing redox signals to proceed in and between cells. Unlike other peroxiporins, human AQP11 is an endoplasmic reticulum (ER)-resident that can conduit H2O2 to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that generates abundant H2O2 during oxidative folding, causes a paradoxical increase in luminal H2O2 levels. The simultaneous AQP11 downregulation prevents this increase, implying that H2O2 reaches the ER from an external source(s). Pharmacological inhibition of the electron transport chain reveals that Ero1α downregulation activates superoxide production by complex III. In the intermembrane space, superoxide dismutase 1 generates H2O2 that enters the ER channeled by AQP11. Meanwhile, the number of ER-mitochondria contact sites increases as well, irrespective of AQP11 expression. Taken together, our findings identify a novel interorganellar redox response that is activated upon Ero1α downregulation and transfers H2O2 from mitochondria to the ER via AQP11.
    Keywords:  Complex III; Hydrogen peroxide; Interorganellar crosstalk/ peroxiporin; Mitochondrial-associated membranes; Redox homeostasis
    DOI:  https://doi.org/10.1016/j.redox.2022.102410
  7. Sci Adv. 2022 Jul 22. 8(29): eabo0155
    The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity.
    Marie Paradis, Nicole Kucharowski, Gabriela Edwards Faret, Santiago José Maya Palacios, Christian Meyer, Birgit Stümpges, Isabell Jamitzky, Julia Kalinowski, Christoph Thiele, Reinhard Bauer, Achim Paululat, Julia Sellin, Margret Helene Bülow.
      Dynamic contacts are formed between endoplasmic reticulum (ER) and mitochondria that enable the exchange of calcium and phospholipids. Disturbed contacts between ER and mitochondria impair mitochondrial dynamics and are a molecular hallmark of Parkinson's disease, which is also characterized by impaired complex I activity and dopaminergic neuron degeneration. Here, we analyzed the role of cysteine-rich with EGF-like domain (Creld), a poorly characterized risk gene for Parkinson's disease, in the regulation of mitochondrial dynamics and function. We found that loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in Drosophila melanogaster, Xenopus tropicalis, and human cells. Creld fly mutants show differences in ER-mitochondria contacts and reduced respiratory complex I activity. The resulting low-hydrogen peroxide levels are linked to disturbed neuronal activity and lead to impaired locomotion, but not neurodegeneration, in Creld mutants. We conclude that Creld regulates ER-mitochondria communication and thereby hydrogen peroxide formation, which is required for normal neuron function.
    DOI:  https://doi.org/10.1126/sciadv.abo0155
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