Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast

Non Miyata, Satoru Fujii, Osamu Kuge

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Mitochondrial synthesis of cardiolipin (CL) and phosphatidylethanolamine requires the transport of their precursors, phosphatidic acid and phosphatidylserine, respectively, to the mitochondrial inner membrane. In yeast, the Ups1-Mdm35 and Ups2-Mdm35 complexes transfer phosphatidic acid and phosphatidylserine, respectively, between the mitochondrial outer and inner membranes. Moreover, a Ups1-independent CL accumulation pathway requires several mitochondrial proteins with unknown functions including Mdm31. Here, we identified a mitochondrial porin, Por1, as a protein that interacts with both Mdm31 and Mdm35 in budding yeast (Saccharomyces cerevisiae). Depletion of the porins Por1 and Por2 destabilized Ups1 and Ups2, decreased CL levels by ∼90%, and caused loss of Ups2-dependent phosphatidylethanolamine synthesis, but did not affect Ups2-independent phosphatidylethanolamine synthesis in mitochondria. Por1 mutations that affected its interactions with Mdm31 and Mdm35, but not respiratory growth, also decreased CL levels. Using HeLa cells, we show that mammalian porins also function in mitochondrial CL metabolism. We conclude that yeast porins have specific and critical functions in mitochondrial phospholipid metabolism and that porin-mediated regulation of CL metabolism appears to be evolutionarily conserved.

Original languageEnglish
Pages (from-to)17593-17605
Number of pages13
JournalThe Journal of biological chemistry
Volume293
Issue number45
DOIs
Publication statusPublished - Nov 9 2018

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Porins
Cardiolipins
Metabolism
Yeast
Phospholipids
Yeasts
Mitochondrial Membranes
Phosphatidic Acids
Proteins
Phosphatidylserines
Membranes
Saccharomycetales
Mitochondria
Mitochondrial Proteins
HeLa Cells
Saccharomyces cerevisiae
Mutation
Growth
phosphatidylethanolamine

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast. / Miyata, Non; Fujii, Satoru; Kuge, Osamu.

In: The Journal of biological chemistry, Vol. 293, No. 45, 09.11.2018, p. 17593-17605.

Research output: Contribution to journalArticle

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