Structure-function insights into direct lipid transfer between membranes by Mmm 1-Mdm 12 of ERMES

Shin Kawano, Yasushi Tamura, Rieko Kojima, Siqin Bala, Eri Asai, Agnès H. Michel, Benoît Kornmann, Isabelle Riezman, Howard Riezman, Yoshitake Sakae, Yuko Okamoto, Toshiya Endo

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER)-mitochondrial encounter structure (ERMES) physically links the membranes of the ER and mitochondria in yeast. Although the ER and mitochondria cooperate to synthesize glycerophospholipids, whether ERMES directly facilitates the lipid exchange between the two organelles remains controversial. Here, we compared the x-ray structures of an ERMES subunit Mdm 12 from Kluyveromyces lactis with that of Mdm 12 from Saccharomyces cerevisiae and found that both Mdm 12 proteins possess a hydrophobic pocket for phospholipid binding. However in vitro lipid transfer assays showed that Mdm 12 alone or an Mmm1 (another ERMES subunit) fusion protein exhibited only a weak lipid transfer activity between liposomes. In contrast, Mdm 12 in a complex with Mmm1 mediated efficient lipid transfer between liposomes. Mutations in Mmm1 or Mdm 12 impaired the lipid transfer activities of the Mdm 12-Mmm1 complex and furthermore caused defective phosphatidylserine transport from the ER to mitochondrial membranes via ERMES in vitro. Therefore, the Mmm 1-Mdm 12 complex functions as a minimal unit that mediates lipid transfer between membranes.

Original languageEnglish
Pages (from-to)959-974
Number of pages16
JournalJournal of Cell Biology
Volume217
Issue number3
DOIs
Publication statusPublished - Mar 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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