Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast

The Journal of Biological Chemistry
Non MiyataOsamu Kuge

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 po...Continue Reading

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Jun 30, 2016·The Journal of Cell Biology·Non MiyataOsamu Kuge

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Citations

Apr 2, 2020·Biological Chemistry·Yasushi TamuraToshiya Endo
Jan 23, 2020·Biological Chemistry·Alexander Grevel, Thomas Becker
Nov 2, 2019·Biochemical Society Transactions·Toshiya Endo, Haruka Sakaue
Sep 5, 2019·Molecular Biology of the Cell·Fenja OdendallKai Stefan Dimmer
Feb 11, 2019·Molecular Cell·Haruka SakaueToshiya Endo
Jul 9, 2021·Journal of Proteome Research·Nikolina ŠoštarićVera van Noort
Sep 11, 2021·ACS Chemical Neuroscience·Altmash KhanRadhakrishnan Mahalakshmi

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