ORP5/8 and MIB/MICOS link ER-mitochondria and intra-mitochondrial contacts for non-vesicular transport of phosphatidylserine.

Autor:	Monteiro-Cardoso VF; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Inserm U1280, 91198 Gif-sur-Yvette Cedex, France., Rochin L; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Inserm U1280, 91198 Gif-sur-Yvette Cedex, France., Arora A; Minerva Foundation Institute for Medical Research, Biomedicum 2U, 00290 Helsinki, Finland., Houcine A; Institut Jacques Monod, CNRS, UMR7592, Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France., Jääskeläinen E; Minerva Foundation Institute for Medical Research, Biomedicum 2U, 00290 Helsinki, Finland., Kivelä AM; Minerva Foundation Institute for Medical Research, Biomedicum 2U, 00290 Helsinki, Finland., Sauvanet C; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Inserm U1280, 91198 Gif-sur-Yvette Cedex, France., Le Bars R; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Imagerie-Gif, Light Microscopy Facility, Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France., Marien E; Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, 3000 Leuven, Belgium., Dehairs J; Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, 3000 Leuven, Belgium., Neveu J; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Inserm U1280, 91198 Gif-sur-Yvette Cedex, France., El Khallouki N; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Inserm U1280, 91198 Gif-sur-Yvette Cedex, France., Santonico E; University of Rome Tor Vergata, via della ricerca scientifica, dipartimento di Biologia, 00133 Roma RM, Italy., Swinnen JV; Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven, 3000 Leuven, Belgium., Tareste D; Université Paris Cité, Inserm UMR-S 1266, Institute of Psychiatry and Neuroscience of Paris (IPNP), Paris, France., Olkkonen VM; Minerva Foundation Institute for Medical Research, Biomedicum 2U, 00290 Helsinki, Finland; Department of Anatomy, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland., Giordano F; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France; Inserm U1280, 91198 Gif-sur-Yvette Cedex, France. Electronic address: francesca.giordano@i2bc.paris-saclay.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Sep 20; Vol. 40 (12), pp. 111364.
DOI:	10.1016/j.celrep.2022.111364
Abstrakt:	Mitochondria are dynamic organelles essential for cell survival whose structural and functional integrity rely on selective and regulated transport of lipids from/to the endoplasmic reticulum (ER) and across the mitochondrial intermembrane space. As they are not connected by vesicular transport, the exchange of lipids between ER and mitochondria occurs at membrane contact sites. However, the mechanisms and proteins involved in these processes are only beginning to emerge. Here, we show that the main physiological localization of the lipid transfer proteins ORP5 and ORP8 is at mitochondria-associated ER membrane (MAM) subdomains, physically linked to the mitochondrial intermembrane space bridging (MIB)/mitochondrial contact sites and cristae junction organizing system (MICOS) complexes that bridge the two mitochondrial membranes. We also show that ORP5/ORP8 mediate non-vesicular transport of phosphatidylserine (PS) lipids from the ER to mitochondria by cooperating with the MIB/MICOS complexes. Overall our study reveals a physical and functional link between ER-mitochondria contacts involved in lipid transfer and intra-mitochondrial membrane contacts maintained by the MIB/MICOS complexes. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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