Substrate- and isoform-specific proteome stability in normal and stressed cardiac mitochondria

Circ Res. 2012 Apr 27;110(9):1174-8. doi: 10.1161/CIRCRESAHA.112.268359. Epub 2012 Mar 27.


Rationale: Mitochondrial protein homeostasis is an essential component of the functions and oxidative stress responses of the heart.

Objective: To determine the specificity and efficiency of proteome turnover of the cardiac mitochondria by endogenous and exogenous proteolytic mechanisms.

Methods and results: Proteolytic degradation of the murine cardiac mitochondria was assessed by 2-dimensional differential gel electrophoresis and liquid chromatography-tandem mass spectrometry. Mitochondrial proteases demonstrated a substrate preference for basic protein variants, which indicates a possible recognition mechanism based on protein modifications. Endogenous mitochondrial proteases and the cytosolic 20S proteasome exhibited different substrate specificities.

Conclusions: The cardiac mitochondrial proteome contains low amounts of proteases and is remarkably stable in isolation. Oxidative damage lowers the proteolytic capacity of cardiac mitochondria and reduces substrate availability for mitochondrial proteases. The 20S proteasome preferentially degrades specific substrates in the mitochondria and may contribute to cardiac mitochondrial proteostasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme Stability
  • Homeostasis
  • Hydrogen Peroxide / pharmacology
  • Isoenzymes
  • Mice
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Oxidants / pharmacology
  • Oxidative Stress* / drug effects
  • Peptide Hydrolases / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteomics / methods
  • Substrate Specificity
  • Tandem Mass Spectrometry


  • Isoenzymes
  • Mitochondrial Proteins
  • Oxidants
  • Hydrogen Peroxide
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex