Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome

Gajanan Sathe, Sekar Deepha, Narayanappa Gayathri, Madhu Nagappa, Bindu Parayil Sankaran, Arun B. Taly, Tripti Khanna, Akhilesh Pandey, Periyasamy Govindaraj

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalMitochondrion
Volume58
DOIs
StatePublished - May 2021

Keywords

  • COX
  • Ethylmalonic encephalopathy
  • Mitochondria
  • Quantitative proteomics
  • Redox regulation
  • Skeletal muscle

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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