Vps39 is required for ethanolamine-stimulated elevation in mitochondrial phosphatidylethanolamine

Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jun;1865(6):158655. doi: 10.1016/j.bbalip.2020.158655. Epub 2020 Feb 11.


Mitochondrial membrane biogenesis requires the import of phospholipids; however, the molecular mechanisms underlying this process remain elusive. Recent work has implicated membrane contact sites between the mitochondria, endoplasmic reticulum (ER), and vacuole in phospholipid transport. Utilizing a genetic approach focused on these membrane contact site proteins, we have discovered a 'moonlighting' role of the membrane contact site and vesicular fusion protein, Vps39, in phosphatidylethanolamine (PE) transport to the mitochondria. We show that the deletion of Vps39 prevents ethanolamine-stimulated elevation of mitochondrial PE levels without affecting PE biosynthesis in the ER or its transport to other sub-cellular organelles. The loss of Vps39 did not alter the levels of other mitochondrial phospholipids that are biosynthesized ex situ, implying a PE-specific role of Vps39. The abundance of Vps39 and its recruitment to the mitochondria and the ER is dependent on PE levels in each of these organelles, directly implicating Vps39 in the PE transport process. Deletion of essential subunits of Vps39-containing complexes, vCLAMP and HOPS, did not abrogate ethanolamine-stimulated PE elevation in the mitochondria, suggesting an independent role of Vps39 in intracellular PE trafficking. Our work thus identifies Vps39 as a novel player in ethanolamine-stimulated PE transport to the mitochondria.

Keywords: HOPS; Mitochondria; Phosphatidylethanolamine; Phospholipid transport; Vps39; vCLAMP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Ethanolamine / metabolism
  • Gene Knockdown Techniques
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Phosphatidylethanolamines / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transferases (Other Substituted Phosphate Groups) / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Phosphatidylethanolamines
  • Saccharomyces cerevisiae Proteins
  • VAM6 protein, S cerevisiae
  • phosphatidylethanolamine
  • Ethanolamine
  • Transferases (Other Substituted Phosphate Groups)
  • choline-ethanolaminephosphotransferase