哺乳动物线粒体动力学和氧化磷酸化研究进展

doi:10.11843/j.issn.0366-6964.2021.02.001

摘要/Abstract

摘要： 线粒体是一种存在于大多数细胞中具有双层膜结构和流动性的细胞器，是细胞进行有氧呼吸的主要场所，为细胞增殖、迁移和生存提供能量，被称为“能量工厂”。线粒体在细胞死亡、细胞衰老、自噬、脂质合成、钙稳态以及铁平衡等生物过程中均发挥着重要作用，其功能主要由线粒体融合和分裂调节。线粒体融合将有助于ATP的产生，主要由线粒体融合蛋白1（mitofusin-1，Mfn1）、线粒体融合蛋白2（mitofusin-2，Mfn2）以及视神经萎缩蛋白1（optic atrophy 1，OPA1）进行调节；线粒体分裂可促进细胞分裂和有丝分裂，主要由动力相关蛋白1（dynamin-related protein 1，Drp1）、分裂蛋白1（fission 1，Fis1）、线粒体分裂因子（mitochondria fission factor，MFF）以及线粒体动力蛋白49/51（mitochondria dynamin protein 49/51，Mid49/51）进行调节。本文针对线粒体融合和分裂以及氧化磷酸化的分子机制展开讨论，强调线粒体形态和动力学的生物学意义，特别是相关基因和蛋白在动物机体和细胞中的调节机制，并对线粒体动力学和形态学在畜牧学中的研究趋势进行展望，以期为今后线粒体的研究提供参考。

关键词: 线粒体, 融合, 分裂, 氧化磷酸化

Abstract: Mitochondria is an organelle with double layered membrane and fluidity, which is the main place for aerobic respiration of cells and provides energy for cell proliferation, migration and survival, hence it is called “power house”. Mitochondria plays an important role in biological processes such as cell death, cell senescence, autophagy, lipid synthesis, calcium homeostasis and iron balance, etc, and its function is mainly regulated by mitochondrial fusion and fission. ATP production is regulated by mitochondrial fusion related proteins such as mitofusin-1 (Mfn1), mitofusin-2 (Mfn2) and optic atrophy 1 (OPA1). Cell division and mitosis are promoted by mitochondria fission related proteins such as dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitochondria fission factor (MFF) and mitochondria dynamin protein 49/51 (Mid49/51). This review discusses the molecular mechanisms of mitochondrial fusion, fission and oxidative phosphorylation, emphasizes the biological significance of mitochondrial morphology and dynamics, especially the regulation mechanism of mitochondria related genes and proteins in bodys and cells of animals, and prospects the research trends of mitochondrial dynamics and morphology in animal husbandry, which will provides a reference for mitochondrial research.

Key words: mitochondria, fusion, fission, oxidative phosphorylation

中图分类号:

Q244
S852.2

文禹粱, 刘秀, 王继卿, 胡江, 罗玉柱, 李少斌. 哺乳动物线粒体动力学和氧化磷酸化研究进展[J]. 畜牧兽医学报, 2021, 52(2): 273-285.

WEN Yuliang, LIU Xiu, WANG Jiqing, HU Jiang, LUO Yuzhu, LI Shaobin. Research Progress of Mitochondrial Dynamics and Oxidative Phosphorylation in Mammal[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(2): 273-285.

参考文献 112

[1]	SARASTE M.Oxidative phosphorylation at the fin de siècle[J].Science,1999,283(5407):1488-1493.
[2]	KRAMER P,BRESSAN P.Our (mother's) mito-chondria and our mind[J].Perspect Psychol Sci,2018, 13(1):88-100.
[3]	KOTIADIS V N,DUCHEN M R,OSELLAME L D.Mitochondrial quality control and communications with the nucleus are important in maintaining mito-chondrial function and cell health[J].Biochim Biophys Acta,2014, 1840(4):1254-1265.
[4]	LUDTMANN M H R,ABRAMOV A Y.Mito-chondrial calcium imbalance in Parkinson's disease[J].Neurosci Lett,2018,663:86-90.
[5]	TOYOKUNI S,ITO F,YAMASHITA K,et al.Iron and thiol redox signaling in cancer:an exquisite balance to escape ferroptosis[J].Free Radic Biol Med,2017,108:610-626.
[6]	LOPEZ J,TAIT S W G.Mitochondrial apoptosis:killing cancer using the enemy within[J].Br J Cancer,2015,112(6):957-962.
[7]	DORN Ⅱ G W,KITSIS R N.The mitochondrial dynamism-mitophagy-cell death interactome:multiple roles performed by members of a mitochondrial molecular ensemble[J].Circ Res,2015,116(1):167-182.
[8]	HORBAY R,BILYY R.Mitochondrial dynamics during cell cycling[J].Apoptosis,2016,21(12):1327-1335.
[9]	NUNNARI J,WONG E D,MEEUSEN S,et al.Studying the behavior of mitochondria[J].Methods Enzymol, 2002,351:381-393.
[10]	ARCHER S L.Mitochondrial dynamics——mito-chondrial fission and fusion in human diseases[J].N Engl J Med, 2013,369(23):2236-2251.
[11]	WAI T,LANGER T.Mitochondrial dynamics and metabolic regulation[J].Trends Endocrinol Metab,2016, 27(2):105-117.
[12]	JOAQUIM M,ESCOBAR-HENRIQUES M.Role of mitofusins and mitophagy in life or death decisions[J]. Front Cell Dev Biol,2020,8:572182.
[13]	YANG W Y.Optogenetic probing of mitochondrial damage responses[J].Ann N Y Acad Sci,2015, 1350(1):48-51.
[14]	RAMOS E S,LARSSON N G,MOURIER A.Bioenergetic roles of mitochondrial fusion[J].Biochim Biophys Acta,2016,1857(8):1277-1283.
[15]	TWIG G,ELORZA A,MOLINA A J A,et al.Fission and selective fusion govern mitochondrial segregation and elimination by autophagy[J].EMBO J,2008,27(2):433-446.
[16]	TOBORE T O.On the central role of mitochondria dysfunction and oxidative stress in Alzheimer's disease[J]. Neurol Sci,2019,40(8):1527-1540.
[17]	VÖLGYI K,BADICS K,SIALANA F J,et al.Early presymptomatic changes in the proteome of mitochondria-associated membrane in the APP/PS1 mouse model of Alzheimer's disease[J].Mol Neurobiol, 2018,55(10):7839-7857.
[18]	NGUYEN M,WONG Y C,YSSELSTEIN D,et al.Synaptic,mitochondrial,and lysosomal dysfunction in Parkinson's disease[J].Trends Neurosci,2019,42(2):140-149.
[19]	LIU Y,MA X P,FUJIOKA H,et al.DJ-1 regulates the integrity and function of ER-mitochondria association through interaction with IP3R3-Grp75-VDAC1[J].Proc Natl Acad Sci U S A,2019,116(50):25322-25328.
[20]	BAYNE A N,TREMPE J F.Mechanisms of PINK1,ubiquitin and Parkin interactions in mitochondrial quality control and beyond[J].Cell Mol Life Sci,2019,76(23):4589-4611.
[21]	ROCHA A G,FRANCO A,KREZEL A M,et al.MFN2 agonists reverse mitochondrial defects in pre-clinical models of Charcot-Marie-Tooth disease type 2A[J].Science,2018,360(6386):336-341.
[22]	LARREA D,PERA M,GONNELLI A,et al.MFN2 mutations in Charcot-Marie-Tooth disease alter mito-chondria-associated ER membrane function but do not impair bioenergetics[J].Hum Mol Genet,2019, 28(11):1782-1800.
[23]	HAM M,HAN J,OSANN K,et al.Meta-analysis of genotype-phenotype analysis of OPA1 mutations in autosomal dominant optic atrophy[J].Mitochondrion,2019,46:262-269.
[24]	JONG C J,YEUNG J,TSEUNG E,et al.Leptin-induced cardiomyocyte hypertrophy is associated with enhanced mitochondrial fission[J].Mol Cell Biochem,2019,454(1-2):33-44.
[25]	DURAISAMY A J,MOHAMMAD G,KOWLURU R A.Mitochondrial fusion and maintenance of mitochondrial homeostasis in diabetic retinopathy[J].Biochim Biophys Acta,2019,1865(6):1617-1626.
[26]	LEE H J,MOON J,CHUNG I,et al.ATP synthase inhibitory factor 1(IF1),a novel myokine,regulates glucose metabolism by AMPK and Akt dual pathways[J].FASEB J,2019,33(12):14825-14840.
[27]	GAZIEV A I,ABDULLAEV S,PODLUTSKY A.Mitochondrial function and mitochondrial DNA maintenance with advancing age[J].Biogerontology,2014,15(5):417-438.
[28]	WANG G,HE Y Y,LUO Y Z.Expression of OPA1 and Mic60 genes and their association with mito-chondrial cristae morphology in Tibetan sheep[J].Cell Tissue Res,2019,376(2):273-279.
[29]	SLOAT S R,WHITLEY B N,ENGELHART E A,et al.Identification of a mitofusin specificity region that confers unique activities to Mfn1 and Mfn2[J].Mol Biol Cell,2019,30(17):2309-2319.
[30]	CHANDHOK G,LAZAROU M,NEUMANN B.Structure,function,and regulation of mitofusin-2 in health and disease[J].Biol Rev Camb Philos Soc,2018,93(2):933-949.
[31]	OANH N T K,PARK Y Y,CHO H.Mitochondria elongation is mediated through SIRT1-mediated MFN1 stabilization[J].Cell Signal,2017,38:67-75.
[32]	BASSO V,MARCHESAN E,PEGGION C,et al.Regulation of ER-mitochondria contacts by Parkin via Mfn2[J].Pharmacol Res,2018,138:43-56.
[33]	CHEN K H,GUO X M,MA D L,et al.Dysregulation of HSG triggers vascular proliferative disorders[J].Nat Cell Biol,2004,6(9):872-883.
[34]	KOSHIBA T,DETMER S A,KAISER J T,et al.Structural basis of mitochondrial tethering by mito-fusin complexes[J].Science,2004,305(5685):858-862.
[35]	DEL DOTTO V,FOGAZZA M,CARELLI V,et al.Eight human OPA1 isoforms,long and short:what are they for?[J].Biochim Biophys Acta,2018,1859(4):263-269.
[36]	ANNESLEY S J,FISHER P R.Mitochondria in health and disease[J].Cells,2019,8(7):680.
[37]	TWIG G,SHIRIHAI O S.The interplay between mitochondrial dynamics and mitophagy[J].Antioxid Redox Signal,2011,14(10):1939-1951.
[38]	LITTLE A C,KOVALENKO I,GOO L E,et al.High-content fluorescence imaging with the metabolic flux assay reveals insights into mitochondrial properties and functions[J].Commun Biol,2020,3(1):271.
[39]	MITRA K,WUNDER C,ROYSAM B,et al.A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase[J].Proc Natl Acad Sci U S A,2009,106(29):11960-11965.
[40]	LIU R H,JIN P P,YU L Q,et al.Impaired mitochondrial dynamics and bioenergetics in diabetic skeletal muscle[J]. PLoS One,2014,9(3):e92810.
[41]	ZHANG Z,CUI D,ZHANG T,et al.Swimming differentially affects T2DM-induced skeletal muscle ER stress and mitochondrial dysfunction related to MAM[J].Diabetes Metab Syndr Obes,2020,13:1417-1428.
[42]	GOMES L C,BENEDETTO G D,SCORRANO L.During autophagy mitochondria elongate,are spared from degradation and sustain cell viability[J].Nat Cell Biol,2011,13(5):589-598.
[43]	LEE J Y,KAPUR M,LI M,et al.MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria[J].J Cell Sci,2014,127(Pt 22):4954-4963.
[44]	TONDERA D,GRANDEMANGE S,JOURDAIN A,et al.SLP-2 is required for stress-induced mitochondrial hyperfusion[J].EMBO J,2009,28(11):1589-1600.
[45]	FARMER T,NASLAVSKY N,CAPLAN S.Tying trafficking to fusion and fission at the mighty mito-chondria[J]. Traffic,2018,19(8):569-577.
[46]	FUJIOKA H,TANDLER B,HOPPEL C L.Mitochondrial division in rat cardiomyocytes:an electron microscope study[J].Anat Rec (Hoboken),2012,295(9):1455-1461.
[47]	KAMERKAR S C,KRAUS F,SHARPE A J,et al.Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission[J].Nat Commun,2018,9(1):5239.
[48]	YU R,JIN S B,LENDAHL U,et al.Human Fis1 regulates mitochondrial dynamics through inhibition of the fusion machinery[J].EMBO J,2019,38(8):e99748.
[49]	YU R,LIU T,NING C F,et al.The phosphorylation status of Ser-637 in dynamin-related protein 1(Drp1) does not determine Drp1 recruitment to mitochondria[J].J Biol Chem,2019,294(46):17262-17277.
[50]	CHEN K H,DASGUPTA A,LIN J H,et al.Epi-genetic dysregulation of the dynamin-related protein 1 binding partners MiD49 and MiD51 increases mitotic mitochondrial fission and promotes pulmonary arterial hypertension:mechanistic and therapeutic implications[J].Circulation,2018,138(3):287-304.
[51]	SCARPELLI P H,TESSARIN-ALMEIDA G,VIÇOSO K L,et al.Melatonin activates FIS1,DYN1,and DYN2Plasmodium falciparum related-genes for mitochondria fission:mitoemerald-GFP as a tool to visualize mitochondria structure[J].J Pineal Res,2019,66(2):e12484.
[52]	ETXEBARRIA A,TERRONES O,YAMAGUCHI H,et al.Endophilin B1/Bif-1 stimulates BAX activation independently from its capacity to produce large scale membrane morphological rearrangements[J].J Biol Chem, 2009,284(7):4200-4212.
[53]	RZEPNIKOWSKA W,KOCHAŃSKI A.A role for the GDAP1 gene in the molecular pathogenesis of Charcot-Marie-Tooth disease[J].Acta Neurobiol Exp (Wars),2018,78(1):1-13.
[54]	XIAO L,XIAN H X,LEE K Y,et al.Death-associated protein 3 regulates mitochondrial-encoded protein synthesis and mitochondrial dynamics[J].J Biol Chem,2015,290(41):24961-24974.
[55]	AUNG L H H,LI Y Z,YU H,et al.Mitochondrial protein 18 is a positive apoptotic regulator in cardiomyocytes under oxidative stress[J].Clin Sci (Lond),2019,133(9):1067-1084.
[56]	PAGLIUSO A,COSSART P,STAVRU F.The ever-growing complexity of the mitochondrial fission machinery[J]. Cell Mol Life Sci,2018,75(3):355-374.
[57]	ZHANG L,ZHAO P H,YUE C P,et al.Sustained release of bioactive hydrogen by Pd hydride nano-particles overcomes Alzheimer's disease[J].Biomaterials,2019,197:393-404.
[58]	PENNANEN C,PARRA V,LÓPEZ-CRISOSTO C,et al.Mitochondrial fission is required for cardiomyocyte hypertrophy mediated by a Ca2+-calcineurin signaling pathway[J].J Cell Sci,2014,127(Pt 12):2659-2671.
[59]	FRIEDMAN J R,LACKNER L L,WEST M,et al.ER tubules mark sites of mitochondrial division[J].Science, 2011,334(6054):358-362.
[60]	KORNMANN B,CURRIE E,COLLINS S R,et al.An ER-mitochondria tethering complex revealed by a synthetic biology screen[J].Science,2009,325(5939):477-481.
[61]	DE BRITO O M,SCORRANO L.Mitofusin 2 tethers endoplasmic reticulum to mitochondria[J].Nature, 2008,456(7222):605-610.
[62]	HIRABAYASHI Y,KWON S K,PAEK H,et al.ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons[J].Science,2017,358(6363):623-630.
[63]	FRIEDMAN J R,WEBSTER B M,MASTRONARDE D N,et al.ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules[J].J Cell Biol,2010,190(3):363-375.
[64]	KOROBOVA F,RAMABHADRAN V,HIGGS H N.An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2[J].Science,2013,339(6118):464-467.
[65]	MEARS J A,LACKNER L L,FANG S M,et al.Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission[J].Nat Struct Mol Biol,2011,18(1):20-26.
[66]	LOSÓN O C,SONG Z Y,CHEN H,et al.Fis1,Mff,MiD49,and MiD51 mediate Drp1 recruitment in mitochondrial fission[J].Mol Biol Cell,2013,24(5):659-667.
[67]	OTERA H,WANG C X,CLELAND M M,et al.Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells[J].J Cell Biol,2010,191(6):1141-1158.
[68]	PALMER C S,OSELLAME L D,LAINE D,et al.MiD49 and MiD51,new components of the mito-chondrial fission machinery[J].EMBO Rep,2011,12(6):565-573.
[69]	ZHAO J,LIU T,JIN S B,et al.Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission[J].EMBO J,2011,30(14):2762-2778.
[70]	FRÖHLICH C,GRABIGER S,SCHWEFEL D,et al.Structural insights into oligomerization and mito-chondrial remodelling of dynamin 1-like protein[J].EMBO J,2013,32(9):1280-1292.
[71]	GONZÁLEZ-JAMETT A M,MOMBOISSE F,HARO-ACUÑA V,et al.Dynamin-2 function and dys-function along the secretory pathway[J].Front Endocrinol (Lausanne),2013,4:126.
[72]	FERGUSON S M,DE CAMILLI P.Dynamin,a membrane-remodelling GTPase[J].Nat Rev Mol Cell Biol,2012, 13(2):75-88.
[73]	LEE J E,WESTRATE L M,WU H X,et al.Multiple dynamin family members collaborate to drive mito-chondrial division[J].Nature,2016,540(7631):139-143.
[74]	HAN X J,LU Y F,LI S A,et al.CaM kinase Iα-induced phosphorylation of Drp1 regulates mito-chondrial morphology[J].J Cell Biol,2008,182(3):573-585.
[75]	BO T,YAMAMORI T,SUZUKI M,et al.Calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) mediates radiation-induced mitochondrial fission by regulating the phosphorylation of dynamin-related protein 1(Drp1) at serine 616[J].Biochem Biophys Res,2018,495(2):1601-1607.
[76]	MOLINA A J A,WIKSTROM J D,STILES L,et al.Mitochondrial networking protects β-cells from nutrient-induced apoptosis[J].Diabetes,2009,58(10):2303-2315.
[77]	MAI N,CHRZANOWSKA-LIGHTOWLERS Z M A,LIGHTOWLERS R N.The process of mammalian mitochondrial protein synthesis[J].Cell Tissue Res,2017,367(1):5-20.
[78]	WASILEWSKI M,CHOJNACKA K,CHACINSKA A.Protein trafficking at the crossroads to mito-chondria[J]. Biochim Biophys Acta,2017,1864(1):125-137.
[79]	CHABAN Y,BOEKEMA E J,DUDKINA N V.Structures of mitochondrial oxidative phosphorylation supercomplexes and mechanisms for their stabilisation[J].Biochim Biophys Acta,2014,1837(4):418-426.
[80]	BARADARAN R,BERRISFORD J M,MINHAS G S,et al.Crystal structure of the entire respiratory complex I[J].Nature,2013,494(7438):443-448.
[81]	EFREMOV R G,BARADARAN R,SAZANOV L A.The architecture of respiratory complex I[J].Nature, 2010, 465(7297):441-445.
[82]	GUERRERO-CASTILLO S,BAERTLING F,KOWNATZKI D,et al.The assembly pathway of mitochondrial respiratory chain complex I[J].Cell Metab,2017,25(1):128-139.
[83]	YANKOVSKAYA V,HORSEFIELD R,TÖRNROTH S,et al.Architecture of succinate dehydrogenase and reactive oxygen species generation[J].Science,2003,299(5607):700-704.
[84]	SUN F,HUO X,ZHAI Y J,et al.Crystal structure of mitochondrial respiratory membrane protein complex Ⅱ[J].Cell,2005,121(7):1043-1057.
[85]	SOUSA J S,D'IMPRIMA E,VONCK J.Mitochondrial respiratory chain complexes[M]//HARRIS J,BOEKEMA E. Membrane Protein Complexes:Structure and Function.Singapore:Springer,2018:167-227.
[86]	IWATA S,LEE J W,OKADA K,et al.Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex[J].Science,1998,281(5373):64-71.
[87]	CROFTS A R,HOLLAND J T,VICTORIA D,et al.The Q-cycle reviewed:how well does a monomeric mechanism of the bc1 complex account for the function of a dimeric complex?[J].Biochim Biophys Acta, 2008,1777(7-8):1001-1019.
[88]	BOTTANI E,CERUTTI R,HARBOUR M E,et al.TTC19 plays a husbandry role on UQCRFS1 turnover in the biogenesis of mitochondrial respiratory complex Ⅲ[J].Mol Cell,2017,67(1):96-105.e4.
[89]	BAREL O,SHORER Z,FLUSSER H,et al.Mitochondrial complex Ⅲ deficiency associated with a homozygous mutation in UQCRQ[J].Am J Hum Genet,2008,82(5):1211-1216.
[90]	ROGER A J,MUÑOZ-GÓMEZ S A,KAMIKAWA R.The origin and diversification of mitochondria[J].Curr Biol,2017,27(21):R1177-R1192.
[91]	BALSA E,MARCO R,PERALES-CLEMENTE E,et al.NDUFA4 is a subunit of complex IV of the mammalian electron transport chain[J].Cell Metab,2012,16(3):378-386.
[92]	KADENBACH B.Regulation of mammalian 13-subunit cytochrome c oxidase and binding of other proteins:role of NDUFA4[J].Trends Endocrinol Metab,2017,28(11):761-770.
[93]	FORNUSKOVA D,STIBUREK L,WENCHICH L,et al.Novel insights into the assembly and function of human nuclear-encoded cytochrome c oxidase subunits 4,5a,6a,7a and 7b[J].Biochem J,2010,428(3):363-374.
[94]	HÜTTEMANN M,KADENBACH B,GROSSMAN L I.Mammalian subunit IV isoforms of cytochrome c oxidase[J].Gene,2001,267(1):111-123.
[95]	SINKLER C A,KALPAGE H,SHAY J,et al.Tissue- and condition-specific isoforms of mammalian cytochrome c oxidase subunits:from function to human disease[J].Oxid Med Cell Longev,2017,2017:1534056.
[96]	ZHOU A N,ROHOU A,SCHEP D G,et al.Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM[J].eLife,2015,4:e10180.
[97]	WALKER J E.The ATP synthase:the understood,the uncertain and the unknown[J].Biochem Soc Trans,2013, 41(1):1-16.
[98]	JONCKHEERE A I,SMEITINK J A M,RODENBURG R J T.Mitochondrial ATP synthase:architecture, function and pathology[J].J Inherit Metab Dis,2012,35(2):211-225.
[99]	GUO R Y,GU J K,ZONG S,et al.Structure and mechanism of mitochondrial electron transport chain[J].Biomed J,2018,41(1):9-20.
[100]	MOURIER A,MATIC S,RUZZENENTE B,et al.The respiratory chain supercomplex organization is independent of COX7a2l isoforms[J].Cell Metab,2014,20(6):1069-1075.
[101]	SCHÄGGER H.Respiratory chain supercomplexes of mitochondria and bacteria[J].Biochim Biophys Acta, 2002, 1555(1-3):154-159.
[102]	LIU F,LÖSSL P,RABBITTS B M,et al.The interactome of intact mitochondria by cross-linking mass spectrometry provides evidence for coexisting respiratory supercomplexes[J].Mol Cell Proteomics,2018, 17(2):216-232.
[103]	SIGNES A,FERNANDEZ-VIZARRA E.Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes[J].Essays Biochem,2018,62(3):255-270.
[104]	GUO R Y,ZONG S,WU M,et al.Architecture of human mitochondrial respiratory megacomplex I2Ⅲ2IV2[J]. Cell,2017,170(6):1247-1257.e12.
[105]	GU J K,WU M,GUO R Y,et al.The architecture of the mammalian respirasome[J].Nature,2016, 537(7622):639-643.
[106]	LETTS J A,FIEDORCZUK K,SAZANOV L A.The architecture of respiratory supercomplexes[J].Nature, 2016,537(7622):644-648.
[107]	BARRIENTOS A,UGALDE C.I function,therefore I am:overcoming skepticism about mitochondrial supercomplexes[J]. Cell Metab,2013,18(2):147-149.
[108]	LAPUENTE-BRUN E,MORENO-LOSHUERTOS R,ACÍN-PÉREZ R,et al.Supercomplex assembly determines electron flux in the mitochondrial electron transport chain[J].Science,2013,340(6140):1567-1570.
[109]	MORENO-LASTRES D,FONTANESI F,GARCÍA-CONSUEGRA I,et al.Mitochondrial complex I plays an essential role in human respirasome assembly[J].Cell Metab,2012,15(3):324-335.
[110]	FERNÁNDEZ-VIZARRA E,TIRANTI V,ZEVIANI M.Assembly of the oxidative phosphorylation system in humans:what we have learned by studying its defects[J].Biochim Biophys Acta,2009,1793(1):200-211.
[111]	WILLIAMS E G,WU Y B,JHA P,et al.Systems proteomics of liver mitochondria function[J].Science,2016, 352(6291):aad0189.
[112]	PÉREZ-PÉREZ R,LOBO-JARNE T,MILENKOVIC D,et al.COX7A2L is a mitochondrial complex Ⅲ binding protein that stabilizes the Ⅲ2+IV super-complex without affecting respirasome formation[J].Cell Rep, 2016,16(9):2387-2398.