酵母线粒体的磷脂转运
|
摘要
线粒体是一种由两层膜包被的细胞器,其功能和结构的稳定性取决于线粒体膜上精确的磷脂组成及分布。线粒体膜上的大部分脂类物质由内质网合成,既而转运到线粒体。而部分脂类利用内质网上产生的前体,在线粒体内膜上合成。由此可见,线粒体膜脂的生物合成需要线粒体与内质网以及线粒体外膜(outer mitochondrial membrane, OMM)与内膜(inner mitochondrial membrane, IMM)之间进行大量的脂质转运。目前认为,这种运输过程既可在拴系因子(tether factors)形成的膜结合部位(membrane contact sites, MCSs)内发生,也可借助脂质转运蛋白(lipid transfer proteins, LTPs)完成。近年来,研究者以酵母为对象,建立了多种线粒体磷脂转运(phospholipid trafficking)的模型,这使人们初步理解了线粒体磷脂转运的机制。本综述总结了酵母线粒体磷脂转运的最新发现,并对这些磷脂转运的模型进行了讨论,以期为今后深入了解线粒体脂类代谢提供参考。
Mitochondria are double-membrane organelles, whose function and architecture rely on the precise distribution and composition of phospholipids. The majority of lipids of the mitochondrial membrane are synthesized in the endoplasmic reticulum(ER) and transported to the mitochondria, whereas a portion of lipids are synthesized in the inner membrane of mitochondria from ER-derived precursors. Thus, the biosynthesis of mitochondrial membrane phospholipids requires extensive lipid exchange between the ER and mitochondria as well as between the outer and the inner mitochondrial membranes. This process is thought to occur at membrane contact sites by membrane tether factors or with the aid of lipid transfer proteins. Over recent years, multiple models for lipid trafficking have been established on the basis of the findings from the yeast, thus generating a preliminary insight of the mechanisms controlling mitochondrial lipid trafficking. In this review, we summarize the latest discoveries of mitochondrial phospholipid trafficking and discuss the models of phospholipid trafficking in Saccharomyces cerevisiae, hoping to provide a basis for deep understanding of mitochondrial lipid metabolism in the future.
Mitochondria are double-membrane organelles, whose function and architecture rely on the precise distribution and composition of phospholipids. The majority of lipids of the mitochondrial membrane are synthesized in the endoplasmic reticulum(ER) and transported to the mitochondria, whereas a portion of lipids are synthesized in the inner membrane of mitochondria from ER-derived precursors. Thus, the biosynthesis of mitochondrial membrane phospholipids requires extensive lipid exchange between the ER and mitochondria as well as between the outer and the inner mitochondrial membranes. This process is thought to occur at membrane contact sites by membrane tether factors or with the aid of lipid transfer proteins. Over recent years, multiple models for lipid trafficking have been established on the basis of the findings from the yeast, thus generating a preliminary insight of the mechanisms controlling mitochondrial lipid trafficking. In this review, we summarize the latest discoveries of mitochondrial phospholipid trafficking and discuss the models of phospholipid trafficking in Saccharomyces cerevisiae, hoping to provide a basis for deep understanding of mitochondrial lipid metabolism in the future.
引文
[1] Galluzzi L,Kepp O,Trojel-Hansen C,et al.Mitochondrial control of cellular life,stress,and death[J].Circ Res,2012,111(9):1198-1207
[2] Dolezal P,Likic V,Tachezy J,et al.Evolution of the molecular machines for protein import into mitochondria[J].Science,2006,313(5785):314-318
[3] Monteiro JP,Oliveira PJ,Jurado AS.Mitochondrial membrane lipid remodeling in pathophysiology:a new target for diet and therapeutic interventions[J].Prog Lipid Res,2013,52(4):513-528
[4] Chan DC.Fusion and fission:interlinked processes critical for mitochondrial health[J].Annu Rev Genet,2012,46:265-287
[5] Tuller G,Nemec T,Hrastnik C,et al.Lipid composition of subcellular membranes of an FY1679-derived haploid yeast wild-type strain grown on different carbon sources[J].Yeast,1999,15(14):1555-1564
[6] Martensson CU,Doan KN,Becker T.Effects of lipids on mitochondrial functions[J].Biochim Biophys Acta Mol Cell Biol Lipids,2017,1862(1):102-113
[7] Henry SA,Kohlwein SD,Carman GM.Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae[J].Genetics,2012,190(2):317-349
[8] Sprong H,van der Sluijs P,van Meer G.How proteins move lipids and lipids move proteins[J].Nat Rev Mol Cell Biol,2001,2(7):504-513
[9] Bai J,Pagano RE.Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles[J].Biochemistry,1997,36(29):8840-8848
[10] McLean LR,Phillips MC.Kinetics of phosphatidylcholine and lysophosphatidylcholine exchange between unilamellar vesicles[J].Biochemistry,1984,23(20):4624-4630
[11] Testet E,Laroche-Traineau J,Noubhani A,et al.Ypr140wp,‘the yeast tafazzin’,displays a mitochondrial lysophosphatidylcholine (lyso-PC) acyltransferase activity related to triacylglycerol and mitochondrial lipid synthesis[J].Biochem J,2005,387(Pt 3):617-626
[12] Sugiura A,McLelland GL,Fon EA,et al.A new pathway for mitochondrial quality control:mitochondrial-derived vesicles[J].EMBO J,2014,33(19):2142-2156
[13] Zinser E,Sperka-Gottlieb CD,Fasch EV,et al.Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae[J].J Bacteriol,1991,173(6):2026-2034
[14] Kornmann B,Currie E,Collins SR,et al.An ER-mitochondria tethering complex revealed by a synthetic biology screen[J].Science,2009,325(5939):477-481
[15] Kornmann B,Osman C,Walter P.The conserved GTPase Gem1 regulates endoplasmic reticulum- mitochondria connections[J].Proc Natl Acad Sci U S A,2011,108(34):14151-14156
[16] Alva V,Lupas AN.The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport[J].Biochim Biophys Acta,2016,1861(8 Pt B):913-923
[17] Kawano S,Tamura Y,Kojima R,et al.Structure-function insights into direct lipid transfer between membranes by Mmm1-Mdm12 of ERMES[J].J Cell Biol 2018,217(3):959-974
[18] Ellenrieder L,Opalinski L,Becker L,et al.Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10[J].Nat Commun,2016,7:13021
[19] Endo T,Tamura Y,Kawano S.Phospholipid transfer by ERMES components[J].Aging(Albany),2018,10(4):528-529
[20] Friedman JR,Kannan M,Toulmay A,et al.Lipid homeostasis is maintained by dual targeting of the mitochondrial PE biosynthesis enzyme to the ER[J].Dev Cell,2018,44(2):261-270.e6
[21] Nguyen TT,Lewandowska A,Choi JY,et al.Gem1 and ERMES do not directly affect phosphatidylserine transport from ER to mitochondria or mitochondrial inheritance[J].Traffic,2012,13(6):880-890
[22] Honscher C,Mari M,Auffarth K,et al.Cellular metabolism regulates contact sites between vacuoles and mitochondria[J].Dev Cell,2014,30(1):86-94
[23] Elbaz-Alon Y,Rosenfeld-Gur E,Shinder V,et al.A dynamic interface between vacuoles and mitochondria in yeast[J].Dev Cell,2014,30(1):95-102
[24] Klecker T,Westermann B.Mitochondria are clamped to vacuoles for lipid transport[J].Dev Cell,2014,30(1):1-2
[25] Gonzalez Montoro A,Auffarth K,Honscher C,et al.Vps39 interacts with Tom40 to establish one of two functionally distinct vacuole-mitochondria contact sites[J].Dev Cell,2018,45(5):621-636.e7
[26] John Peter AT,Herrmann B,Antunes D,et al.Vps13-Mcp1 interact at vacuole-mitochondria interfaces and bypass ER-mitochondria contact sites[J].J Cell Biol,2017,216(10):3219-3229
[27] Bean BDM,Dziurdzik SK,Kolehmainen KL,et al.Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites[J].J Cell Biol,2018,217(10):3593-3607
[28] Elbaz-Alon Y,Eisenberg-Bord M,Shinder V,et al.Lam6 regulates the extent of contacts between organelles[J].Cell Rep,2015,12(1):7-14
[29] Gatta AT,Wong LH,Sere YY,et al.A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport[J].Elife,2015,4.doi:10.7754/elife.07253
[30] Murley A,Sarsam RD,Toulmay A,et al.Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts[J].J Cell Biol,2015,209(4):539-548
[31] Voss C,Lahiri S,Young BP,et al.ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S.cerevisiae[J].J Cell Sci,2012,125(Pt 20):4791-4799
[32] Lahiri S,Chao JT,Tavassoli S,et al.A conserved endoplasmic reticulum membrane protein complex (EMC) facilitates phospholipid transfer from the ER to mitochondria[J].PLoS Biol,2014,12(10):e1001969
[33] Jonikas MC,Collins SR,Denic V,et al.Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum[J].Science,2009,323(5922):1693-1697
[34] Yamaji-Hasegawa A,Tsujimoto M.Asymmetric distribution of phospholipids in biomembranes[J].Biol Pharm Bull,2006,29(8):1547-1553
[35] Zinser E,Daum G.Isolation and biochemical characterization of organelles from the yeast,Saccharomyces cerevisiae[J].Yeast,1995,11(6):493-536
[36] Simbeni R,Paltauf F,Daum G.Intramitochondrial transfer of phospholipids in the yeast,Saccharomyces cerevisiae[J].J Biol Chem,1990,265(1):281-285
[37] Harner M,Korner C,Walther D,et al.The mitochondrial contact site complex,a determinant of mitochondrial architecture[J].EMBO J,2011,30(21):4356-4370
[38] van der Laan M,Horvath SE,Pfanner N.Mitochondrial contact site and cristae organizing system[J].Curr Opin Cell Biol,2016,41:33-42
[39] Hoppins S,Collins SR,Cassidy-Stone A,et al.A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria[J].J Cell Biol,2011,195(2):323-340
[40] Rampelt H,Wollweber F,Gerke C,et al.Assembly of the mitochondrial cristae organizer Mic10 is regulated by Mic26-Mic27 antagonism and cardiolipin[J].J Mol Biol,2018,430(13):1883-1890
[41] Aaltonen MJ,Friedman JR,Osman C,et al.MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria[J].J Cell Biol,2016,213(5):525-534
[42] Carman GM,Han GS.Regulation of phospholipid synthesis in the yeast saccharomyces cerevisiae[J].Annu Rev Biochem,2011,80:859-883
[43] Tavassoli S,Chao JT,Young BP,et al.Plasma membrane--endoplasmic reticulum contact sites regulate phosphatidylcholine synthesis[J].EMBO Rep,2013,14(5):434-440
[44] Horvath SE,Bottinger L,Vogtle FN,et al.Processing and topology of the yeast mitochondrial phosphatidylserine decarboxylase 1[J].J Biol Chem,2012,287(44):36744-36755
[45] Potting C,Wilmes C,Engmann T,et al.Regulation of mitochondrial phospholipids by Ups1/PRELI-like proteins depends on proteolysis and Mdm35[J].EMBO J,2010,29(17):2888-2898
[46] Tamura Y,Iijima M,Sesaki H.Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation[J].EMBO J,2010,29(17):2875-2887
[47] Connerth M,Tatsuta T,Haag M,et al.Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein[J].Science,2012,338(6108):815-818
[48] Tamura Y,Endo T,Iijima M,et al.Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria[J].J Cell Biol,2009,185(6):1029-1045
[49] Osman C,Haag M,Potting C,et al.The genetic interactome of prohibitins:coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria[J].J Cell Biol,2009,184(4):583-596
[50] Yu F,He F,Yao H,et al.Structural basis of intramitochondrial phosphatidic acid transport mediated by Ups1-Mdm35 complex[J].EMBO Rep,2015,16(7):813-823
[51] Tamura Y,Onguka O,Hobbs AE,et al.Role for two conserved intermembrane space proteins,Ups1p and Ups2p,[corrected] in intra-mitochondrial phospholipid trafficking[J].J Biol Chem,2012,287(19):15205-15218
[52] Miyata N,Watanabe Y,Tamura Y,et al.Phosphatidylserine transport by Ups2-Mdm35 in respiration- active mitochondria[J].J Cell Biol,2016,214(1):77-88
[2] Dolezal P,Likic V,Tachezy J,et al.Evolution of the molecular machines for protein import into mitochondria[J].Science,2006,313(5785):314-318
[3] Monteiro JP,Oliveira PJ,Jurado AS.Mitochondrial membrane lipid remodeling in pathophysiology:a new target for diet and therapeutic interventions[J].Prog Lipid Res,2013,52(4):513-528
[4] Chan DC.Fusion and fission:interlinked processes critical for mitochondrial health[J].Annu Rev Genet,2012,46:265-287
[5] Tuller G,Nemec T,Hrastnik C,et al.Lipid composition of subcellular membranes of an FY1679-derived haploid yeast wild-type strain grown on different carbon sources[J].Yeast,1999,15(14):1555-1564
[6] Martensson CU,Doan KN,Becker T.Effects of lipids on mitochondrial functions[J].Biochim Biophys Acta Mol Cell Biol Lipids,2017,1862(1):102-113
[7] Henry SA,Kohlwein SD,Carman GM.Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae[J].Genetics,2012,190(2):317-349
[8] Sprong H,van der Sluijs P,van Meer G.How proteins move lipids and lipids move proteins[J].Nat Rev Mol Cell Biol,2001,2(7):504-513
[9] Bai J,Pagano RE.Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles[J].Biochemistry,1997,36(29):8840-8848
[10] McLean LR,Phillips MC.Kinetics of phosphatidylcholine and lysophosphatidylcholine exchange between unilamellar vesicles[J].Biochemistry,1984,23(20):4624-4630
[11] Testet E,Laroche-Traineau J,Noubhani A,et al.Ypr140wp,‘the yeast tafazzin’,displays a mitochondrial lysophosphatidylcholine (lyso-PC) acyltransferase activity related to triacylglycerol and mitochondrial lipid synthesis[J].Biochem J,2005,387(Pt 3):617-626
[12] Sugiura A,McLelland GL,Fon EA,et al.A new pathway for mitochondrial quality control:mitochondrial-derived vesicles[J].EMBO J,2014,33(19):2142-2156
[13] Zinser E,Sperka-Gottlieb CD,Fasch EV,et al.Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae[J].J Bacteriol,1991,173(6):2026-2034
[14] Kornmann B,Currie E,Collins SR,et al.An ER-mitochondria tethering complex revealed by a synthetic biology screen[J].Science,2009,325(5939):477-481
[15] Kornmann B,Osman C,Walter P.The conserved GTPase Gem1 regulates endoplasmic reticulum- mitochondria connections[J].Proc Natl Acad Sci U S A,2011,108(34):14151-14156
[16] Alva V,Lupas AN.The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport[J].Biochim Biophys Acta,2016,1861(8 Pt B):913-923
[17] Kawano S,Tamura Y,Kojima R,et al.Structure-function insights into direct lipid transfer between membranes by Mmm1-Mdm12 of ERMES[J].J Cell Biol 2018,217(3):959-974
[18] Ellenrieder L,Opalinski L,Becker L,et al.Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10[J].Nat Commun,2016,7:13021
[19] Endo T,Tamura Y,Kawano S.Phospholipid transfer by ERMES components[J].Aging(Albany),2018,10(4):528-529
[20] Friedman JR,Kannan M,Toulmay A,et al.Lipid homeostasis is maintained by dual targeting of the mitochondrial PE biosynthesis enzyme to the ER[J].Dev Cell,2018,44(2):261-270.e6
[21] Nguyen TT,Lewandowska A,Choi JY,et al.Gem1 and ERMES do not directly affect phosphatidylserine transport from ER to mitochondria or mitochondrial inheritance[J].Traffic,2012,13(6):880-890
[22] Honscher C,Mari M,Auffarth K,et al.Cellular metabolism regulates contact sites between vacuoles and mitochondria[J].Dev Cell,2014,30(1):86-94
[23] Elbaz-Alon Y,Rosenfeld-Gur E,Shinder V,et al.A dynamic interface between vacuoles and mitochondria in yeast[J].Dev Cell,2014,30(1):95-102
[24] Klecker T,Westermann B.Mitochondria are clamped to vacuoles for lipid transport[J].Dev Cell,2014,30(1):1-2
[25] Gonzalez Montoro A,Auffarth K,Honscher C,et al.Vps39 interacts with Tom40 to establish one of two functionally distinct vacuole-mitochondria contact sites[J].Dev Cell,2018,45(5):621-636.e7
[26] John Peter AT,Herrmann B,Antunes D,et al.Vps13-Mcp1 interact at vacuole-mitochondria interfaces and bypass ER-mitochondria contact sites[J].J Cell Biol,2017,216(10):3219-3229
[27] Bean BDM,Dziurdzik SK,Kolehmainen KL,et al.Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites[J].J Cell Biol,2018,217(10):3593-3607
[28] Elbaz-Alon Y,Eisenberg-Bord M,Shinder V,et al.Lam6 regulates the extent of contacts between organelles[J].Cell Rep,2015,12(1):7-14
[29] Gatta AT,Wong LH,Sere YY,et al.A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport[J].Elife,2015,4.doi:10.7754/elife.07253
[30] Murley A,Sarsam RD,Toulmay A,et al.Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts[J].J Cell Biol,2015,209(4):539-548
[31] Voss C,Lahiri S,Young BP,et al.ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S.cerevisiae[J].J Cell Sci,2012,125(Pt 20):4791-4799
[32] Lahiri S,Chao JT,Tavassoli S,et al.A conserved endoplasmic reticulum membrane protein complex (EMC) facilitates phospholipid transfer from the ER to mitochondria[J].PLoS Biol,2014,12(10):e1001969
[33] Jonikas MC,Collins SR,Denic V,et al.Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum[J].Science,2009,323(5922):1693-1697
[34] Yamaji-Hasegawa A,Tsujimoto M.Asymmetric distribution of phospholipids in biomembranes[J].Biol Pharm Bull,2006,29(8):1547-1553
[35] Zinser E,Daum G.Isolation and biochemical characterization of organelles from the yeast,Saccharomyces cerevisiae[J].Yeast,1995,11(6):493-536
[36] Simbeni R,Paltauf F,Daum G.Intramitochondrial transfer of phospholipids in the yeast,Saccharomyces cerevisiae[J].J Biol Chem,1990,265(1):281-285
[37] Harner M,Korner C,Walther D,et al.The mitochondrial contact site complex,a determinant of mitochondrial architecture[J].EMBO J,2011,30(21):4356-4370
[38] van der Laan M,Horvath SE,Pfanner N.Mitochondrial contact site and cristae organizing system[J].Curr Opin Cell Biol,2016,41:33-42
[39] Hoppins S,Collins SR,Cassidy-Stone A,et al.A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria[J].J Cell Biol,2011,195(2):323-340
[40] Rampelt H,Wollweber F,Gerke C,et al.Assembly of the mitochondrial cristae organizer Mic10 is regulated by Mic26-Mic27 antagonism and cardiolipin[J].J Mol Biol,2018,430(13):1883-1890
[41] Aaltonen MJ,Friedman JR,Osman C,et al.MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria[J].J Cell Biol,2016,213(5):525-534
[42] Carman GM,Han GS.Regulation of phospholipid synthesis in the yeast saccharomyces cerevisiae[J].Annu Rev Biochem,2011,80:859-883
[43] Tavassoli S,Chao JT,Young BP,et al.Plasma membrane--endoplasmic reticulum contact sites regulate phosphatidylcholine synthesis[J].EMBO Rep,2013,14(5):434-440
[44] Horvath SE,Bottinger L,Vogtle FN,et al.Processing and topology of the yeast mitochondrial phosphatidylserine decarboxylase 1[J].J Biol Chem,2012,287(44):36744-36755
[45] Potting C,Wilmes C,Engmann T,et al.Regulation of mitochondrial phospholipids by Ups1/PRELI-like proteins depends on proteolysis and Mdm35[J].EMBO J,2010,29(17):2888-2898
[46] Tamura Y,Iijima M,Sesaki H.Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation[J].EMBO J,2010,29(17):2875-2887
[47] Connerth M,Tatsuta T,Haag M,et al.Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein[J].Science,2012,338(6108):815-818
[48] Tamura Y,Endo T,Iijima M,et al.Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria[J].J Cell Biol,2009,185(6):1029-1045
[49] Osman C,Haag M,Potting C,et al.The genetic interactome of prohibitins:coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria[J].J Cell Biol,2009,184(4):583-596
[50] Yu F,He F,Yao H,et al.Structural basis of intramitochondrial phosphatidic acid transport mediated by Ups1-Mdm35 complex[J].EMBO Rep,2015,16(7):813-823
[51] Tamura Y,Onguka O,Hobbs AE,et al.Role for two conserved intermembrane space proteins,Ups1p and Ups2p,[corrected] in intra-mitochondrial phospholipid trafficking[J].J Biol Chem,2012,287(19):15205-15218
[52] Miyata N,Watanabe Y,Tamura Y,et al.Phosphatidylserine transport by Ups2-Mdm35 in respiration- active mitochondria[J].J Cell Biol,2016,214(1):77-88