ORP5 and ORP8 Orchestrate Lipid Droplet Biogenesis and Maintenance at ER-mitochondria Contact Sites

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2022 Aug 15

PMID 35969857

Authors

Valentin Guyard

Vera Filipa Monteiro-Cardoso

Mohyeddine Omrane

Cecile Sauvanet

Audrey Houcine

Claire Boulogne

Kalthoum Ben Mbarek

Nicolas Vitale

Orestis Faklaris

Naima El Khallouki

Abdou Rachid Thiam

Francesca Giordano

Affiliations

Soon will be listed here.

Abstract

Lipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the endoplasmic reticulum (ER). The ER protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at mitochondria-associated ER membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulates seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis and maturation at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at the membrane contact sites.

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