1. Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome.
- Author
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Sathe G, Deepha S, Gayathri N, Nagappa M, Parayil Sankaran B, Taly AB, Khanna T, Pandey A, and Govindaraj P
- Subjects
- Adult, Brain Diseases, Metabolic, Inborn physiopathology, Down-Regulation, Humans, Male, Oxidative Phosphorylation, Proteomics methods, Purpura physiopathology, Signal Transduction, Brain Diseases, Metabolic, Inborn genetics, Mitochondria, Muscle physiology, Mitochondrial Proteins genetics, Muscle Proteins metabolism, Muscle, Skeletal metabolism, Mutation, Nucleocytoplasmic Transport Proteins genetics, Proteome, Purpura genetics
- Abstract
Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. To study the molecular effects of ETHE1 p. D165H mutation, we employed mass spectrometry-based mitochondrial proteome and phosphoproteome profiling in the human skeletal muscle. Eighty-six differentially altered proteins were identified, of which thirty-seven mitochondrial proteins were differentially expressed, and most of the proteins (37%) were down-regulated in the OXPHOS complex-IV. Also, nine phosphopeptides that correspond to eight mitochondrial proteins were significantly affected in EE patient. These altered proteins recognized are involved in several pathways and molecular functions, predominantly in oxidoreductase activity. This is the first study that has integrated proteome and phosphoproteome of skeletal muscle and identified multiple proteins associated in the pathogenesis of EE., (Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
- Published
- 2021
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