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Proteomics of Cytochrome c Oxidase-Negative versus -Positive Muscle Fiber Sections in Mitochondrial Myopathy.

Abstract
The mosaic distribution of cytochrome c oxidase+ (COX+) and COX- muscle fibers in mitochondrial disorders allows the sampling of fibers with compensated and decompensated mitochondrial function from the same individual. We apply laser capture microdissection to excise individual COX+ and COX- fibers from the biopsies of mitochondrial myopathy patients. Using mass spectrometry-based proteomics, we quantify >4,000 proteins per patient. While COX+ fibers show a higher expression of respiratory chain components, COX- fibers display protean adaptive responses, including upregulation of mitochondrial ribosomes, translation proteins, and chaperones. Upregulated proteins include C1QBP, required for mitoribosome formation and protein synthesis, and STOML2, which organizes cardiolipin-enriched microdomains and the assembly of respiratory supercomplexes. Factoring in fast/slow fiber type, COX- slow fibers show a compensatory upregulation of beta-oxidation, the AAA+ protease AFG3L1, and the OPA1-dependent cristae remodeling program. These findings reveal compensatory mechanisms in muscle fibers struggling with energy shortage and metabolic stress.
AuthorsMarta Murgia, Jing Tan, Philipp E Geyer, Sophia Doll, Matthias Mann, Thomas Klopstock
JournalCell reports (Cell Rep) Vol. 29 Issue 12 Pg. 3825-3834.e4 (Dec 17 2019) ISSN: 2211-1247 [Electronic] United States
PMID31851916 (Publication Type: Journal Article)
CopyrightCopyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Chemical References
  • Proteome
  • Electron Transport Complex IV
Topics
  • Adult
  • Case-Control Studies
  • Computational Biology
  • Electron Transport Complex IV (metabolism)
  • Energy Metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Myopathies (metabolism, pathology)
  • Muscle, Skeletal (metabolism)
  • Proteome (analysis, metabolism)
  • Proteomics (methods)
  • Single-Cell Analysis (methods)
  • Stress, Physiological

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