Protein acetylation in skeletal muscle mitochondria is involved in impaired fatty acid oxidation and exercise intolerance in heart failure

Journal of Cachexia, Sarcopenia and Muscle
Masaya TsudaToshihisa Anzai

Abstract

Exercise intolerance is a common clinical feature and is linked to poor prognosis in patients with heart failure (HF). Skeletal muscle dysfunction, including impaired energy metabolism in the skeletal muscle, is suspected to play a central role in this intolerance, but the underlying mechanisms remain elusive. Lysine acetylation, a recently identified post-translational modification, has emerged as a major contributor to the derangement of mitochondrial metabolism. We thus investigated whether mitochondrial protein acetylation is associated with impaired skeletal muscle metabolism and lowered exercise capacity in both basic and clinical settings of HF. We first conducted a global metabolomic analysis to determine whether plasma acetyl-lysine is a determinant factor for peak oxygen uptake (peak VO2 ) in HF patients. We then created a murine model of HF (n = 11) or sham-operated (n = 11) mice with or without limited exercise capacity by ligating a coronary artery, and we tested the gastrocnemius tissues by using mass spectrometry-based acetylomics. A causative relationship between acetylation and the activity of a metabolic enzyme was confirmed in in vitro studies. The metabolomic analysis verified that acetyl-lysine was the most...Continue Reading

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Citations

Feb 2, 2019·Journal of Cachexia, Sarcopenia and Muscle·Bumsoo AhnHolly Van Remmen
Mar 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yanxiong HuoYixuan Li
Dec 31, 2019·European Heart Journal Supplements : Journal of the European Society of Cardiology·Guilherme Wesley Peixoto da Fonseca, Stephan von Haehling
Jun 2, 2020·Frontiers in Cardiovascular Medicine·Shingo TakadaShintaro Kinugawa
Dec 20, 2020·Journal of Cachexia, Sarcopenia and Muscle·Nadja Scherbakov, Wolfram Doehner
May 9, 2021·BMC Pharmacology & Toxicology·Takaaki FurihataShintaro Kinugawa
Jun 19, 2019·Cardiology·Jiahao DuanLing Yang
Dec 4, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Shingo TakadaShintaro Kinugawa
Dec 28, 2021·European Journal of Heart Failure·Kirsten T NijholtB Daan Westenbrink

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Methods Mentioned

BETA
acetylation
electrophoresis
dissection
transfection
biopsy

Software Mentioned

Proteome
GraphPad Prism
lab
Agilent G2201AA ChemStation
ACTIMO System
Scaffold
Dat
MasterHands
Mascot

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