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

Murgia, Marta; Tan, Jing; Geyer, Philipp E.; Doll, Sophia; Mann, Matthias und Klopstock, Thomas (2019): Proteomics of Cytochrome c Oxidase-Negative versus -Positive Muscle Fiber Sections in Mitochondrial Myopathy. In: Cell Reports, Bd. 29, Nr. 12

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2211-1247
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198