Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast

被引:22
作者
Miyata, Non [1 ]
Fujii, Satoru [1 ]
Kuge, Osamu [1 ]
机构
[1] Kyushu Univ, Dept Chem, Fac Sci, Fukuoka, Fukuoka 8190395, Japan
基金
日本学术振兴会;
关键词
phospholipid; cardiolipin; phosphatidylethanolamine; phosphatidic acid; phosphatidylserine; mitochondria; lipid metabolism; membrane transport; porin; SACCHAROMYCES-CEREVISIAE; INTERMEMBRANE SPACE; PHOSPHATIDYLSERINE DECARBOXYLASE; CARDIOLIPIN SYNTHASE; TRANSPORT; COMPLEX; CLONING; GENE; UPS1P; UPS2-MDM35;
D O I
10.1074/jbc.RA118.005410
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 approximate to 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.
引用
收藏
页码:17593 / 17605
页数:13
相关论文
共 40 条
  • [1] MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria
    Aaltonen, Mari J.
    Friedman, Jonathan R.
    Osman, Christof
    Salin, Benedicte
    Di Rago, Jean-Paul
    Nunnari, Jodi
    Langer, Thomas
    Tatsuta, Takashi
    [J]. JOURNAL OF CELL BIOLOGY, 2016, 213 (05) : 525 - 534
  • [2] Belli G, 1998, YEAST, V14, P1127, DOI 10.1002/(SICI)1097-0061(19980915)14:12<1127::AID-YEA300>3.3.CO
  • [3] 2-R
  • [4] Multicopy suppressors of phenotypes resulting from the absence of yeast VDAC encode a VDAC-like protein
    BlachlyDyson, E
    Song, JM
    Wolfgang, WJ
    Colombini, M
    Forte, M
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (10) : 5727 - 5738
  • [5] BLACHLYDYSON E, 1993, J BIOL CHEM, V268, P1835
  • [6] Isolation and characterization of the gene (CLS1) encoding cardiolipin synthase in Saccharomyces cerevisiae
    Chang, SC
    Heacock, PN
    Mileykovskaya, E
    Voelker, DR
    Dowhan, W
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (24) : 14933 - 14941
  • [7] Recombinant Human Voltage Dependent Anion Selective Channel Isoform 3 (hVDAC3) Forms Pores with a Very Small Conductance
    Checchetto, Vanessa
    Reina, Simona
    Magri, Andrea
    Szabo, Ildiko
    De Pinto, Vito
    [J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2014, 34 (03) : 842 - 853
  • [8] CLANCEY CJ, 1993, J BIOL CHEM, V268, P24580
  • [9] Intramitochondrial Transport of Phosphatidic Acid in Yeast by a Lipid Transfer Protein
    Connerth, Melanie
    Tatsuta, Takashi
    Haag, Mathias
    Klecker, Till
    Westermann, Benedikt
    Langer, Thomas
    [J]. SCIENCE, 2012, 338 (6108) : 815 - 818
  • [10] Daum G, 1998, YEAST, V14, P1471, DOI 10.1002/(SICI)1097-0061(199812)14:16<1471::AID-YEA353>3.0.CO