bims-mecosi 2021-12-12 papers

bims-mecosi

Biomed News

on Membrane contact sites

Issue of 2021–12–12
seven papers selected by
Verena Kohler, Stockholm University

Peroxisomal Membrane Contact Sites in Yeasts.
Cholesterol transport in the late endocytic pathway: Roles of ORP family proteins.
Reduction of ER-Mitochondria Distance: a Key Feature in Alzheimer's and Parkinson's Disease, and During Cancer Treatment.
Molecular species selectivity of lipid transport creates a mitochondrial sink for di-unsaturated phospholipids.
Lunapark-dependent formation of a virus-induced ER exit site contains multi-tubular ER junctions that promote viral ER-to-cytosol escape.
TAOK2 is an ER-localized kinase that catalyzes the dynamic tethering of ER to microtubules.
Differential Effects of Oleic and Palmitic Acids on Lipid Droplet-Mitochondria Interaction in the Hepatic Cell Line HepG2.

Front Cell Dev Biol. 2021 ;9 735031

Peroxisomal Membrane Contact Sites in Yeasts.

Amit S Joshi.

  Peroxisomes are ubiquitous, single membrane-bound organelles that play a crucial role in lipid metabolism and human health. While peroxisome number is maintained by the division of existing peroxisomes, nascent peroxisomes can be generated from the endoplasmic reticulum (ER) membrane in yeasts. During formation and proliferation, peroxisomes maintain membrane contacts with the ER. In addition to the ER, contacts between peroxisomes and other organelles such as lipid droplets, mitochondria, vacuole, and plasma membrane have been reported. These membrane contact sites (MCS) are dynamic and important for cellular function. This review focuses on the recent developments in peroxisome biogenesis and the functional importance of peroxisomal MCS in yeasts.

Keywords:  endoplasmic reticulum; lipid droplet; membrane contact sites; mitochondria; organelles; peroxisomes

DOI:  https://doi.org/10.3389/fcell.2021.735031
J Steroid Biochem Mol Biol. 2021 Dec 02. pii: S0960-0760(21)00233-8. [Epub ahead of print] 106040

Cholesterol transport in the late endocytic pathway: Roles of ORP family proteins.

Vesa M Olkkonen, Elina Ikonen.

  Oxysterol-binding protein (OSBP) homologues, designated ORP or OSBPL proteins, constitute one of the largest families of intracellular lipid-binding/transfer proteins (LTP). This review summarizes the mounting evidence that several members of this family participate in the machinery facilitating cholesterol trafficking in the late endocytic pathway. There are indications that OSBP, besides acting as a cholesterol/phosphatidylinositol 4-phosphate (PI4P) exchanger at the endoplasmic reticulum (ER)-trans-Golgi network (TGN) membrane contact sites (MCS), also exchanges these lipids at ER-lysosome (Lys) contacts, increasing Lys cholesterol content. The long isoform of ORP1 (ORP1 L), which also targets ER-late endosome (LE)/Lys MCS, has the capacity to mediate cholesterol transport either from ER to LE or in the opposite direction. Moreover, it regulates the motility, positioning and fusion of LE as well as autophagic flux. ORP2, the closest relative of ORP1, is mainly cytosolic, but also targets PI(4,5)P2-rich endosomal compartments. Our latest data suggest that ORP2 transfers cholesterol from LE to recycling endosomes (RE) in exchange for PI(4,5)P2, thus stimulating the recruitment of focal adhesion kinase (FAK) on the RE and cell adhesion. FAK activates phosphoinositide kinase on the RE to enhance PI(4,5)P2 synthesis. ORP2 in turn transfers PI(4,5)P2 from RE to LE, thus regulating LE tubule formation and transport activity.

Keywords:  cholesterol; late endosome; lipid transport; lysosome; membrane contact site; phosphoinositide

DOI:  https://doi.org/10.1016/j.jsbmb.2021.106040
Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021 4412-4415

Reduction of ER-Mitochondria Distance: a Key Feature in Alzheimer's and Parkinson's Disease, and During Cancer Treatment.

Carmen A Perez-Leanos, Hugo E Romero-Campos, Genevieve Dupont, Virginia Gonzalez-Velez.

One remarkable dynamic cell structure is the region between the endoplasmic reticulum (ER) and the mitochondria, termed the mitochondria-associated membranes (MAM). MAMs carry out different cellular functions such as Ca2+ homeostasis and lipid synthesis, which depend on an adequate distance separating the ER and mitochondria. A decreased distance has been observed in Alzheimer's disease, Parkinson's disease, and during cancer treatment. It is unclear how dysregulation of the spatial characteristics of MAMs can cause abnormal Ca2+ dynamics which could end in cell death. In this work, a computational model was proposed to study the relationship between a decreased ER-mitochondria distance and mitochondria-induced cell death. Our results point towards the mitochondrial permeability transition pore (mPTP) as a key cell death signaling mechanism indirectly regulated by the spatial characteristics of MAMs.Clinical Relevance- The endoplasmic reticulum-mitochondria crosstalk plays an important role in the mPTP-induced apoptosis. This process could be behind neurodegeneration in Alzheimer's and Parkinson's diseases, as well as behind the induced cell death during cancer treatment.

DOI: https://doi.org/10.1109/EMBC46164.2021.9631090
EMBO J. 2021 Dec 07. e106837

Molecular species selectivity of lipid transport creates a mitochondrial sink for di-unsaturated phospholipids.

Mike F Renne, Xue Bao, Margriet Wj Hokken, Adolf S Bierhuizen, Martin Hermansson, Richard R Sprenger, Tom A Ewing, Xiao Ma, Ruud C Cox, Jos F Brouwers, Cedric H De Smet, Christer S Ejsing, Anton Ipm de Kroon.

  Mitochondria depend on the import of phospholipid precursors for the biosynthesis of phosphatidylethanolamine (PE) and cardiolipin, yet the mechanism of their transport remains elusive. A dynamic lipidomics approach revealed that mitochondria preferentially import di-unsaturated phosphatidylserine (PS) for subsequent conversion to PE by the mitochondrial PS decarboxylase Psd1p. Several protein complexes tethering mitochondria to the endomembrane system have been implicated in lipid transport in yeast, including the endoplasmic reticulum (ER)-mitochondrial encounter structure (ERMES), ER-membrane complex (EMC), and the vacuole and mitochondria patch (vCLAMP). By limiting the availability of unsaturated phospholipids, we created conditions to investigate the mechanism of lipid transfer and the contributions of the tethering complexes in vivo. Under these conditions, inactivation of ERMES components or of the vCLAMP component Vps39p exacerbated accumulation of saturated lipid acyl chains, indicating that ERMES and Vps39p contribute to the mitochondrial sink for unsaturated acyl chains by mediating transfer of di-unsaturated phospholipids. These results support the concept that intermembrane lipid flow is rate-limited by molecular species-dependent lipid efflux from the donor membrane and driven by the lipid species' concentration gradient between donor and acceptor membrane.

Keywords:  lipid transport; membrane contact sites; membrane lipid homeostasis; membrane lipid unsaturation; mitochondria

DOI:  https://doi.org/10.15252/embj.2020106837
Cell Rep. 2021 Dec 07. pii: S2211-1247(21)01568-0. [Epub ahead of print]37(10): 110077

Lunapark-dependent formation of a virus-induced ER exit site contains multi-tubular ER junctions that promote viral ER-to-cytosol escape.

Parikshit Bagchi, Xiaofang Liu, Woo Jung Cho, Billy Tsai.

  Viruses rearrange host membranes to support different entry steps. Polyomavirus simian virus 40 (SV40) reorganizes the endoplasmic reticulum (ER) membrane to generate focus structures that enable virus ER-to-cytosol escape, a decisive infection step. The molecular architecture of the ER exit site that might illuminate why it is ideally suited for membrane penetration is unknown. Here 3D focused ion beam scanning electron microscopy (FIB-SEM) reconstruction reveals that the ER focus structure consists of multi-tubular ER junctions where SV40 preferentially localizes, suggesting that tubular branch points are virus ER-to-cytosol penetration sites. Functional analysis demonstrates that lunapark-an ER membrane protein that typically stabilizes three-way ER junctions-relocates to the ER foci, where it supports focus formation, leading to SV40 ER escape and infection. Our results reveal how a virus repurposes the activity of an ER membrane protein to form a virus-induced ER substructure required for membrane escape and suggest that ER tubular junctions are vulnerable sites exploited by viruses for membrane penetration.

Keywords:  Endoplasmid reticulum; FIB-SEM; Lunapark; Membrane trafficking; Non-enveloped virus; Polyomavirus; SV40

DOI:  https://doi.org/10.1016/j.celrep.2021.110077
Dev Cell. 2021 Dec 04. pii: S1534-5807(21)00939-4. [Epub ahead of print]

TAOK2 is an ER-localized kinase that catalyzes the dynamic tethering of ER to microtubules.

Kimya Nourbakhsh, Amy A Ferreccio, Matthew J Bernard, Smita Yadav.

  The endoplasmic reticulum (ER) depends on extensive association with the microtubule (MT) cytoskeleton for its structure and mitotic inheritance. However, mechanisms that underlie coupling of ER membranes to MTs are poorly understood. We have identified thousand and one amino acid kinase 2 (TAOK2) as a pleiotropic protein kinase that mediates tethering of ER to MTs. In human cells, TAOK2 localizes in distinct ER subdomains via transmembrane helices and an adjacent amphipathic region. Through its C-terminal tail, TAOK2 directly binds MTs, coupling ER membranes to the MT cytoskeleton. In TAOK2 knockout cells, although ER-membrane dynamics are increased, movement of ER along growing MT plus ends is disrupted. ER-MT tethering is tightly regulated by catalytic activity of TAOK2, perturbation of which leads to defects in ER morphology, association with MTs, and cell division. Our study identifies TAOK2 as an ER-MT tether and reveals a kinase-regulated mechanism for control of ER dynamics.

Keywords:  ER kinase; TAOK2; endoplasmic reticulum; organelle-cytoskeletal tethering

DOI:  https://doi.org/10.1016/j.devcel.2021.11.015
Front Nutr. 2021 ;8 775382

Differential Effects of Oleic and Palmitic Acids on Lipid Droplet-Mitochondria Interaction in the Hepatic Cell Line HepG2.

Andrea Eynaudi, Francisco Díaz-Castro, Juan Carlos Bórquez, Roberto Bravo-Sagua, Valentina Parra, Rodrigo Troncoso.

  Fatty acid overload, either of the saturated palmitic acid (PA) or the unsaturated oleic acid (OA), causes triglyceride accumulation into specialized organelles termed lipid droplets (LD). However, only PA overload leads to liver damage mediated by mitochondrial dysfunction. Whether these divergent outcomes stem from differential effects of PA and OA on LD and mitochondria joint dynamics remains to be uncovered. Here, we contrast how both fatty acids impact the morphology and interaction between both organelles and mitochondrial bioenergetics in HepG2 cells. Using confocal microscopy, we showed that short-term (2-24 h) OA overload promotes more and bigger LD accumulation than PA. Oxygen polarography indicated that both treatments stimulated mitochondrial respiration; however, OA favored an overall build-up of the mitochondrial potential, and PA evoked mitochondrial fragmentation, concomitant with an ATP-oriented metabolism. Even though PA-induced a lesser increase in LD-mitochondria proximity than OA, those LD associated with highly active mitochondria suggest that they interact mainly to fuel fatty acid oxidation and ATP synthesis (that is, metabolically "active" LD). On the contrary, OA overload seemingly stimulated LD-mitochondria interaction mainly for LD growth (thus metabolically "passive" LDs). In sum, these differences point out that OA readily accumulates in LD, likely reducing their toxicity, while PA preferably stimulates mitochondrial oxidative metabolism, which may contribute to liver damage progression.

Keywords:  fatty acids; hepatocytes; lipid droplets; mitochondria; oxygen consumption

DOI:  https://doi.org/10.3389/fnut.2021.775382