ORP5/ORP8 localize to endoplasmic reticulum-mitochondria contacts and are involved in mitochondrial function

EMBO Rep. 2016 Jun;17(6):800-10. doi: 10.15252/embr.201541108. Epub 2016 Apr 13.

Abstract

The oxysterol-binding protein (OSBP)-related proteins ORP5 and ORP8 have been shown recently to transport phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM) at ER-PM contact sites. PS is also transferred from the ER to mitochondria where it acts as precursor for mitochondrial PE synthesis. Here, we show that, in addition to ER-PM contact sites, ORP5 and ORP8 are also localized to ER-mitochondria contacts and interact with the outer mitochondrial membrane protein PTPIP51. A functional lipid transfer (ORD) domain was required for this localization. Interestingly, ORP5 and ORP8 depletion leads to defects in mitochondria morphology and respiratory function.

Keywords: ORP; endoplasmic reticulum; lipid transfer proteins; membrane contact sites; mitochondria.

MeSH terms

  • Cell Line
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Gene Knockdown Techniques
  • Humans
  • Lipid Metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Transport
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*

Substances

  • Mitochondrial Proteins
  • Receptors, Steroid
  • oxysterol binding protein
  • Protein Tyrosine Phosphatases
  • RMDN3 protein, human