Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints

doi:10.1152/ajpendo.00088.2019

	Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints
	Kappler, Lisa 1; Hoene, Miriam 1; Hu, Chunxiu 2; von Toerne, Christine 3; Li, Jia 1,4; Bleher, Daniel 1; Hoffmann, Christoph 1; Boehm, Anja 5,6; Kollipara, Laxmikanth 7; Zischka, Hans 8,9
刊名	AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
	2019-08-01
卷号	317 期号:2 页码:E374-E387
关键词	cardiolipins liver mitochondria multi-omics muscle
ISSN号	0193-1849
DOI	10.1152/ajpendo.00088.2019
通讯作者	Lehmann, Rainer(rainer.lehmann@med.uni-tuebingen.de)
英文摘要	Mitochondria are dynamic organelles with diverse functions in tissues such as liver and skeletal muscle. To unravel the mitochondrial contribution to tissue-specific physiology, we performed a systematic comparison of the mitochondrial proteome and lipidome of mice and assessed the consequences hereof for respiration. Liver and skeletal muscle mitochondrial protein composition was studied by data-independent ultra-high-performance (UHP)LC-MS/MS-proteomics, and lipid profiles were compared by UIIPLC-MS/MS lipidomics. Mitochondrial function was investigated by high-resolution respirometry in samples from mice and humans. Enzymes of pyruvate oxidation as well as several subunits of complex I, III, and ATP synthase were more abundant in muscle mitochondria. Muscle mitochondria were enriched in cardiolipins associated with higher oxidative phosphorylation capacity and flexibility, in particular CL(18:2)(4) and 22:6-containing cardiolipins. In contrast, protein equipment of liver mitochondria indicated a shuttling of complex I substrates toward gluconeogenesis and ketogenesis and a higher preference for electron transfer via the flavoprotein quinone oxidoreductase pathway. Concordantly, muscle and liver mitochondria showed distinct respiratory substrate preferences. Muscle respired significantly more on the complex I substrates pyruvate and glutamate, whereas in liver maximal respiration was supported by complex II substrate succinate. This was a consistent finding in mouse liver and skeletal muscle mitochondria and human samples. Muscle mitochondria are tailored to produce ATP with a high capacity for complex I-linked substrates. Liver mitochondria are more connected to biosynthetic pathways, preferring fatty acids and succinate for oxidation. The physiologic diversity of mitochondria may help to understand tissue-specific disease pathologies and to develop therapies targeting mitochondrial function.
资助项目	Alexander von Humboldt Foundation ; German Federal Ministry of Education and Research (BMBF)[01GI0925] ; National Key Research and Development Program of China[2017YFC0906900] ; National Natural Science Foundation of China[21874130] ; National Natural Science Foundation of China[21435006] ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; BMBF
WOS关键词	SKELETAL-MUSCLE ; RESPIRATORY-CHAIN ; OXIDATIVE-PHOSPHORYLATION ; SUPERCOMPLEX FORMATION ; LINOLEIC-ACID ; CARDIOLIPIN ; LIVER ; PHOSPHOLIPIDS ; GLUCONEOGENESIS ; DYSFUNCTION
WOS研究方向	Endocrinology & Metabolism ; Physiology
语种	英语
出版者	AMER PHYSIOLOGICAL SOC
WOS记录号	WOS:000481599900011
资助机构	Alexander von Humboldt Foundation ; Alexander von Humboldt Foundation ; German Federal Ministry of Education and Research (BMBF) ; German Federal Ministry of Education and Research (BMBF) ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; BMBF ; BMBF ; Alexander von Humboldt Foundation ; Alexander von Humboldt Foundation ; German Federal Ministry of Education and Research (BMBF) ; German Federal Ministry of Education and Research (BMBF) ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; BMBF ; BMBF ; Alexander von Humboldt Foundation ; Alexander von Humboldt Foundation ; German Federal Ministry of Education and Research (BMBF) ; German Federal Ministry of Education and Research (BMBF) ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; BMBF ; BMBF ; Alexander von Humboldt Foundation ; Alexander von Humboldt Foundation ; German Federal Ministry of Education and Research (BMBF) ; German Federal Ministry of Education and Research (BMBF) ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; Regierende Burgermeister von Berlin - inkl. Wissenschaft und Forschung ; BMBF ; BMBF
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/173523]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Lehmann, Rainer
作者单位	1.Univ Hosp Tuebingen, Inst Clin Chem & Pathobiochem, Dept Diagnost Lab Med, Hoppe Seyler Str 3, D-72076 Tubingen, Germany 2.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China 3.Helmholtz Ctr Munich, Res Unit Prot Sci, Munich, Germany 4.Chinese Acad Agr Sci, Tea Res Inst, Minist Agr, Key Lab Tea Biol & Resources Utilizat, Hangzhou, Zhejiang, Peoples R China 5.Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany 6.German Ctr Diabet Res, Tubingen, Germany 7.Leibniz Inst Analyt Wissensch ISAS, Dortmund, Germany 8.German Res Ctr Environm Hlth GmbH, Helmholtz Ctr Munich, Inst Mol Toxicol & Pharmacol, Neuherberg, Germany 9.Tech Univ Munich, Inst Toxicol & Environm Hyg, Munich, Germany 10.Univ Hosp Tuebingen, Dept Gen Visceral & Transplant Surg, Tubingen, Germany
推荐引用方式 GB/T 7714	Kappler, Lisa,Hoene, Miriam,Hu, Chunxiu,et al. Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints[J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM,2019,317(2):E374-E387.
APA	Kappler, Lisa.,Hoene, Miriam.,Hu, Chunxiu.,von Toerne, Christine.,Li, Jia.,...&Lehmann, Rainer.(2019).Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints.AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM,317(2),E374-E387.
MLA	Kappler, Lisa,et al."Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints".AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 317.2(2019):E374-E387.