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

Autor: David Tareste, Vera F Monteiro-Cardoso, Francesca Giordano, Audrey Houcine, Annukka M. Kivelä, Eyra Marien, Romain Le Bars, Naima El Khallouki, Elena Santonico, Eeva Jääskeläinen, Leila Rochin, Vesa M. Olkkonen, Johannes V. Swinnen, Jonas Dehairs, Amita Arora, Julie Neveu, Cécile Sauvanet
Rok vydání: 2021
Předmět:
Zdroj: Cell reports. 40(12)
ISSN: 2211-1247
Popis: 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. ispartof: CELL REPORTS vol:40 issue:12 ispartof: location:United States status: published
Databáze: OpenAIRE