Molecular Species Selectivity of Lipid Transport Creates a Mitochondrial Sink for Di-unsaturated Phospholipids

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2021 Dec 7

PMID 34873731

Citations 12

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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