Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale

Cell Rep. 2017 Jun 27;19(13):2836-2852. doi: 10.1016/j.celrep.2017.06.014.


Mitochondria perform central functions in cellular bioenergetics, metabolism, and signaling, and their dysfunction has been linked to numerous diseases. The available studies cover only part of the mitochondrial proteome, and a separation of core mitochondrial proteins from associated fractions has not been achieved. We developed an integrative experimental approach to define the proteome of yeast mitochondria. We classified > 3,300 proteins of mitochondria and mitochondria-associated fractions and defined 901 high-confidence mitochondrial proteins, expanding the set of mitochondrial proteins by 82. Our analysis includes protein abundance under fermentable and nonfermentable growth, submitochondrial localization, single-protein experiments, and subcellular classification of mitochondria-associated fractions. We identified mitochondrial interactors of respiratory chain supercomplexes, ATP synthase, AAA proteases, the mitochondrial contact site and cristae organizing system (MICOS), and the coenzyme Q biosynthesis cluster, as well as mitochondrial proteins with dual cellular localization. The integrative proteome provides a high-confidence source for the characterization of physiological and pathophysiological functions of mitochondria and their integration into the cellular environment.

Keywords: SILAC; dual localization; mitochondria; protein copy numbers; protein-protein interaction; quantitative MS; subcellular localization; submitochondrial localization.

MeSH terms

  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Proteomics / methods*