Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart.
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.
Wang
Jun
J
Department of Cardiology, First Affiliated Hospital ofMedical College of Xi'an Jiaotong University, Xi'an, China.
Bai
Ling
L
Li
Jing
J
Sun
ChaoFeng
C
Zhao
Jin
J
Cui
ChangCong
C
Han
Ke
K
Liu
Yu
Y
Zhuo
XiaoZhen
X
Wang
TingZhong
T
Liu
Ping
P
Fan
FenLing
F
Guan
YouFei
Y
Ma
AiQun
A
D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size; D010084:Oxidation-Reduction; D020543:Proteome / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005227:Fatty Acids; D024101:Mitochondrial Proteins; D020543:Proteome