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Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart

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Abstract

This work characterizes the mitochondrial proteomic profile in the failing heart and elucidates the molecular basis of mitochondria in heart failure. Heart failure was induced in rats by myocardial infarction, and mitochondria were isolated from hearts by differential centrifugation. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, a system biology approach was employed to investigate differences in mitochondrial proteins between normal and failing hearts. Mass spectrometry identified 27 proteins differentially expressed that involved in energy metabolism. Among those, the up-regulated proteins included tricarboxylic acid cycle enzymes and pyruvate dehydrogenase complex subunits while the down-regulated proteins were involved in fatty acid oxidation and the OXPHOS complex. These results suggest a substantial metabolic switch from free fatty acid oxidation to glycolysis in heart failure and provide molecular evidence for alterations in the structural and functional parameters of mitochondria that may contribute to cardiac dysfunction during ischemic injury.

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Abbreviations

PCr:

phosphocreatine

ANT:

adenine nucleotide translocator

CHAPS:

3-[(3-cholamidopropyl)-dimethyammonio]-1-propane sulfate

DTT:

dithiothreitol

SDS:

Sodium dodecyl sulfate

HEPES:

N-2-Hydroxyethylpiperazine-N′-2′-ethanesu lfonic acid

EDTA:

ethylenediamine tetraacetic acid

EGTA:

ethyleneglycol bis (2-aminoethyl ether) tetraacetic acid

PMSF:

phenylmethyl sulfonylfluoride

TEMED:

N,N,N′,N′-Tetramethylethylenediamine

IPG:

immobilized pH gradient

MALDITOF-MS:

matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy

PMF:

peptide mass fingerprinting

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Authors and Affiliations

  1. Department of Cardiology, First affiliated hospital of medical college of Xi’an Jiaotong University, Xi’an, 710061, China

    Jun Wang, Ling Bai, ChaoFeng Sun, Jin Zhao, ChangCong Cui, Ke Han, Yu Liu, XiaoZhen Zhuo, TingZhong Wang, Ping Liu, FenLing Fan & AiQun Ma

  2. Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi’an, 710061, China

    Jun Wang, Ling Bai, ChaoFeng Sun, ChangCong Cui, Ke Han, Yu Liu, XiaoZhen Zhuo, TingZhong Wang, Ping Liu, FenLing Fan & AiQun Ma

  3. Department of Physiology and Pathophysiology; Key Laboratory of Molecular Cardiovascular Sciences of the Ministry of Education, Peking University Health Science Center, Beijing, 100083, China

    Jing Li & YouFei Guan

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  1. Jun Wang
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  2. Ling Bai
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Correspondence to AiQun Ma.

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Supported by the National Natural Science Foundation of China (Grant No. 3030036)

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Wang, J., Bai, L., Li, J. et al. Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart. SCI CHINA SER C 52, 1003–1010 (2009). https://doi.org/10.1007/s11427-009-0140-2

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  • DOI: https://doi.org/10.1007/s11427-009-0140-2

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