期刊
METABOLISM-CLINICAL AND EXPERIMENTAL
卷 89, 期 -, 页码 18-26出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2018.09.006
关键词
Subsarcolemmal; Intermyofibrillar; Adiposity; Mass spectrometry; Proteome
资金
- National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01DK094062]
Background: Skeletal muscle mitochondrial content and function appear to be altered in obesity. Mitochondria in muscle are found in well-defined regions within cells, and they are arranged in a way that form distinct subpopulations of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. We sought to investigate differences in the proteomes of SS and IMF mitochondria between lean subjects and subjects with obesity. Methods: We performed comparative proteomic analyses on SS and IMF mitochondria isolated from muscle samples obtained from lean subjects and subjects with obesity. Mitochondria were isolated using differential centrifugation, and proteins were subjected to label-free quantitative tandem mass spectrometry analyses. Collected data were evaluated for abundance of mitochondrial proteins using spectral counting. The Reactome pathway database was used to determine metabolic pathways that are altered in obesity. Results: Among proteins, 73 and 41 proteins showed different (mostly lower) expression in subjects with obesity ill the SS and IMF mitochondria, respectively (false discovery rate-adjusted P <= 0.05). We specifically found an increase in proteins forming the tricarboxylic acid cycle and electron transport chain (ETC) complex II, but a decrease in proteins forming protein complexes I and III of the ETC and adenosine triphosphate (ATP) synthase in subjects with obesity in the IMF, but not SS, mitochondria. Obesity was associated with differential effects on metabolic pathways linked to protein translation in the SS mitochondria and ATP formation in the IMF mitochondria. Conclusions: Obesity alters the expression of mitochondrial proteins regulating key metabolic processes in skeletal muscle, and these effects are distinct to mitochondrial subpopulations located in different regions of the muscle fibers. Trial Registration: ClinicalTrials.gov (NCT01824173). (C) 2018 Elsevier Inc. All rights reserved.
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