The Fusogenic Lipid Phosphatidic Acid Promotes the Biogenesis of Mitochondrial Outer Membrane Protein Ugo1

J Cell Biol. 2015 Sep 14;210(6):951-60. doi: 10.1083/jcb.201506085.

Abstract

Import and assembly of mitochondrial proteins depend on a complex interplay of proteinaceous translocation machineries. The role of lipids in this process has been studied only marginally and so far no direct role for a specific lipid in mitochondrial protein biogenesis has been shown. Here we analyzed a potential role of phosphatidic acid (PA) in biogenesis of mitochondrial proteins in Saccharomyces cerevisiae. In vivo remodeling of the mitochondrial lipid composition by lithocholic acid treatment or by ablation of the lipid transport protein Ups1, both leading to an increase of mitochondrial PA levels, specifically stimulated the biogenesis of the outer membrane protein Ugo1, a component of the mitochondrial fusion machinery. We reconstituted the import and assembly pathway of Ugo1 in protein-free liposomes, mimicking the outer membrane phospholipid composition, and found a direct dependency of Ugo1 biogenesis on PA. Thus, PA represents the first lipid that is directly involved in the biogenesis pathway of a mitochondrial membrane protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Liposomes
  • Lithocholic Acid / pharmacology
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / biosynthesis*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Phosphatidic Acids / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / biosynthesis*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Liposomes
  • Membrane Proteins
  • Mitochondrial Proteins
  • Phosphatidic Acids
  • Saccharomyces cerevisiae Proteins
  • UGO1 protein, S cerevisiae
  • Ups1 protein, S cerevisiae
  • Lithocholic Acid