Mass-spectrometry-based proteomics reveals mitochondrial supercomplexome plasticity

Alba Gonzalez-Franquesa, Ben Stocks, Sabina Chubanava, Helle B. Hattel, Roger Moreno-Justicia, Lone Peijs, Jonas T. Treebak, Juleen R. Zierath, Atul S. Deshmukh*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

33 Citations (Scopus)
65 Downloads (Pure)

Abstract

Mitochondrial respiratory complex subunits assemble in supercomplexes. Studies of supercomplexes have typically relied upon antibody-based quantification, often limited to a single subunit per respiratory complex. To provide a deeper insight into mitochondrial and supercomplex plasticity, we combine native electrophoresis and mass spectrometry to determine the supercomplexome of skeletal muscle from sedentary and exercise-trained mice. We quantify 422 mitochondrial proteins within 10 supercomplex bands in which we show the debated presence of complexes II and V. Exercise-induced mitochondrial biogenesis results in non-stoichiometric changes in subunits and incorporation into supercomplexes. We uncover the dynamics of supercomplex-related assembly proteins and mtDNA-encoded subunits after exercise. Furthermore, exercise affects the complexing of Lactb, an obesity-associated mitochondrial protein, and ubiquinone biosynthesis proteins. Knockdown of ubiquinone biosynthesis proteins leads to alterations in mitochondrial respiration. Our approach can be applied to broad biological systems. In this instance, comprehensively analyzing respiratory supercomplexes illuminates previously undetectable complexity in mitochondrial plasticity.

Original languageEnglish
Article number109180
JournalCell Reports
Volume35
Issue number8
Number of pages20
ISSN2211-1247
DOIs
Publication statusPublished - 2021

Keywords

  • CYTOCHROME-C-OXIDASE
  • RESPIRATORY-CHAIN
  • SKELETAL-MUSCLE
  • COMPLEX-I
  • COENZYME-Q
  • ELECTRON-TRANSFER
  • EXERCISE PERFORMANCE
  • METABOLIC PATHWAYS
  • ENERGY-METABOLISM
  • PROTEIN COMPLEXES

Cite this