Vps39 is required for ethanolamine-stimulated elevation in mitochondrial phosphatidylethanolamine

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1865; no. 6; p. 158655
• Main Authors: Iadarola, Donna M., Basu Ball, Writoban, Trivedi, Prachi P., Fu, Guo, Nan, Beiyan, Gohil, Vishal M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2020
• Subjects: biogenesis; biosynthesis; endoplasmic reticulum; HOPS; Mitochondria; mitochondrial membrane; Phosphatidylethanolamine; phosphatidylethanolamines; Phospholipid transport; proteins; vacuoles; vCLAMP; Vps39; Mitochondria; Phosphatidylethanolamine; PE; vCLAMP; HOPS; Phospholipid transport; ERMES; Etn; Vps39
• ISSN: 1388-1981; 1879-2618; 1879-2618
• DOI: 10.1016/j.bbalip.2020.158655

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. •Vps39 is required for ethanolamine stimulated PE transport to yeast mitochondria.•The role of Vps39 in PE transport is independent of HOPS and vCLAMP complexes.•Vps39 abundance is reduced in cells lacking mitochondrial PE biosynthetic enzyme.•The Kennedy pathway enzyme for PE synthesis, Ept1, localizes to the ER.