bims-mecosi 2023-04-30 papers

Issue of 2023‒04‒30
five papers selected by
Verena Kohler

Toxins (Basel). 2023 Mar 30. pii: 253. [Epub ahead of print]15(4):

Inhibition of Mitochondrial Fission Alleviates Zearalenone-Induced Mitochondria-Associated Endoplasmic Reticulum Membrane Dysfunction in Piglet Sertoli Cells.

Li Ma, Chuangjiang Chen, Sirao Hai, Chenlong Wang, Sajid Ur Rahman, Wanyue Huang, Chang Zhao, Shibin Feng, Xichun Wang.

This study aimed to investigate the effects of zearalenone (ZEA) on piglet Sertoli cell (SC)-mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) based on mitochondrial fission, and to explore the molecular mechanism of ZEA-induced cell damage. After the SCs were exposed to the ZEA, the cell viability decreased, the Ca2+ levels increased, and the MAM showed structural damage. Moreover, glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1) were upregulated at the mRNA and protein levels. However, phosphofurin acidic cluster protein 2 (PACS2), mitofusin2 (Mfn2), voltage-dependent anion channel 1 (VDAC1), and inositol 1,4,5-trisphosphate receptor (IP3R) were downregulated at the mRNA and protein levels. A pretreatment with mitochondrial division inhibitor 1 (Mdivi-1) decreased the ZEA-induced cytotoxicity toward the SCs. In the ZEA + Mdivi-1 group, the cell viability increased, the Ca2+ levels decreased, the MAM damage was repaired, and the expression levels of Grp75 and Miro1 decreased, while those of PACS2, Mfn2, VDAC1, and IP3R increased compared with those in the ZEA-only group. Thus, ZEA causes MAM dysfunction in piglet SCs through mitochondrial fission, and mitochondria can regulate the ER via MAM.

Keywords: mitochondria-associated endoplasmic-reticulum membrane; mitochondrial fission; piglet Sertoli cells; zearalenone

DOI: https://doi.org/10.3390/toxins15040253

Biochim Biophys Acta Mol Cell Res. 2023 Apr 23. pii: S0167-4889(23)00046-0. [Epub ahead of print] 119475

Phosphatidylinositol 4,5-bisphosphate and calcium at ER-PM junctions - Complex interplay of simple messengers.

Adelina Ivanova, Peace Atakpa-Adaji.

Endoplasmic reticulum-plasma membrane contact sites (ER-PM MCS) are a specialised domain involved in the control of Ca2+ dynamics and various Ca2+-dependent cellular processes. Intracellular Ca2+ signals are broadly supported by Ca2+ release from intracellular Ca2+ channels such as inositol 1,4,5-trisphosphate receptors (IP3Rs) and subsequent store-operated Ca2+ entry (SOCE) across the PM to replenish store content. IP3Rs sit in close proximity to the PM where they can easily access newly synthesised IP3, interact with binding partners such as actin, and localise adjacent to ER-PM MCS populated by the SOCE machinery, STIM1-2 and Orai1-3, to possibly form a locally regulated unit of Ca2+ influx. PtdIns(4,5)P2 is a multiplex regulator of Ca2+ signalling at the ER-PM MCS interacting with multiple proteins at these junctions such as actin and STIM1, whilst also being consumed as a substrate for phospholipase C to produce IP3 in response to extracellular stimuli. In this review, we consider the mechanisms regulating the synthesis and turnover of PtdIns(4,5)P2 via the phosphoinositide cycle and its significance for sustained signalling at the ER-PM MCS. Furthermore, we highlight recent insights into the role of PtdIns(4,5)P2 in the spatiotemporal organization of signalling at ER-PM junctions and raise outstanding questions on how this multi-faceted regulation occurs.

Keywords: Ca(2+); IP(3) receptor; Membrane contact sites; Phosphoinositide metabolism; PtdIns(4,5)P(2); Store-operated Ca(2+) entry

DOI: https://doi.org/10.1016/j.bbamcr.2023.119475

Contact (Thousand Oaks). 2022 Jan-Dec;5:5

Autophagy of the ER requires actin assembly driven by the interaction of ER with endocytic pits.

Peter Novick, Dongmei Liu, Susan Ferro-Novick.

Autophagy of the cortical ER in budding yeast was unexpectedly found to require End3, a component of the endocytic machinery that promotes the assembly of actin at endocytic pits on the plasma membrane. The cortical ER transiently interacts with invaginating endocytic pits through a linkage consisting of VAP proteins, oxysterol binding proteins and type I myosins. These proteins are required for actin assembly and for autophagy of the ER. Assembly of actin at these contact sites may direct the movement of ER away from the cortex towards sites of autophagosome assembly.

Keywords: VAP; actin assembly; autophagy; autophagy receptor; endocytosis; endoplasmic reticulum

DOI: https://doi.org/10.1177/25152564221093215

J Phys Chem Lett. 2023 Apr 28. 4172-4178

The Nanometer-Scale Proximity of Bilayers Facilitates Intermembrane Lipid Transfer.

Ayari Miyajima, Hiroyuki Nakao, Keisuke Ikeda, Minoru Nakano.

Biological membranes approach one another in various biological phenomena, such as lipid transport at membrane contact sites and membrane fusion. The proximity of two bilayers may cause environmental changes in the interbilayer space and alter the dynamics of lipid molecules. Here, we investigate the structure and dynamics of vesicles aggregated due to the depletion attraction caused by polyethylene glycol (PEG) through static and dynamic small-angle neutron scattering. Manipulation of the interbilayer distance using PEG-conjugated lipids reveals that lipid molecules rapidly transfer between vesicles when the opposing bilayers are within ∼2 nm of each other. This distance corresponds to a region in which water molecules are more structured than in bulk water. Kinetic analysis suggests that the decrease in water entropy is responsible for the progression of lipid transfer. These results provide a basis for understanding the dynamic function of biomembranes in confined regions.

DOI: https://doi.org/10.1021/acs.jpclett.3c00154

J Cell Biol. 2023 Jul 03. pii: e202211039. [Epub ahead of print]222(7):

Parallel phospholipid transfer by Vps13 and Atg2 determines autophagosome biogenesis dynamics.

Rahel Dabrowski, Susanna Tulli, Martin Graef.

During autophagy, rapid membrane assembly expands small phagophores into large double-membrane autophagosomes. Theoretical modeling predicts that the majority of autophagosomal phospholipids are derived from highly efficient non-vesicular phospholipid transfer (PLT) across phagophore-ER contacts (PERCS). Currently, the phagophore-ER tether Atg2 is the only PLT protein known to drive phagophore expansion in vivo. Here, our quantitative live-cell imaging analysis reveals a poor correlation between the duration and size of forming autophagosomes and the number of Atg2 molecules at PERCS of starving yeast cells. Strikingly, we find that Atg2-mediated PLT is non-rate limiting for autophagosome biogenesis because membrane tether and the PLT protein Vps13 localizes to the rim and promotes the expansion of phagophores in parallel with Atg2. In the absence of Vps13, the number of Atg2 molecules at PERCS determines the duration and size of forming autophagosomes with an apparent in vivo transfer rate of ∼200 phospholipids per Atg2 molecule and second. We propose that conserved PLT proteins cooperate in channeling phospholipids across organelle contact sites for non-rate-limiting membrane assembly during autophagosome biogenesis.

DOI: https://doi.org/10.1083/jcb.202211039