Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase. Academic Article uri icon

Overview

abstract

  • Mitochondria are double-membrane-bounded organelles that depend critically on phospholipids supplied by the endoplasmic reticulum. These lipids must cross the outer membrane to support mitochondrial function, but how they do this is unclear. We identify the Voltage Dependent Anion Channel (VDAC), an abundant outer membrane protein, as a scramblase-type lipid transporter that catalyzes lipid entry. On reconstitution into membrane vesicles, dimers of human VDAC1 and VDAC2 catalyze rapid transbilayer translocation of phospholipids by a mechanism that is unrelated to their channel activity. Coarse-grained molecular dynamics simulations of VDAC1 reveal that lipid scrambling occurs at a specific dimer interface where polar residues induce large water defects and bilayer thinning. The rate of phospholipid import into yeast mitochondria is an order of magnitude lower in the absence of VDAC homologs, indicating that VDACs provide the main pathway for lipid entry. Thus, VDAC isoforms, members of a superfamily of beta barrel proteins, moonlight as a class of phospholipid scramblases - distinct from alpha-helical scramblase proteins - that act to import lipids into mitochondria.

publication date

  • December 8, 2023

Research

keywords

  • Phospholipids
  • Voltage-Dependent Anion Channel 1

Identity

PubMed Central ID

  • PMC10709637

Digital Object Identifier (DOI)

  • 10.1038/s41467-023-43570-y

PubMed ID

  • 38065946

Additional Document Info

volume

  • 14

issue

  • 1