title: Substrate- and isoform-specific proteome stability in normal and stressed cardiac mitochondria.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Lau
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Yu
authors.forename: Maggie P Y
authors.initials: MP
authors.lastname: Lam
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Liang
authors.forename: Nobel
authors.initials: N
authors.lastname: Zong
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Peipei
authors.initials: P
authors.lastname: Ping
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004795:Enzyme Stability; D006706:Homeostasis; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes; D051379:Mice; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D007527:Isoenzymes; D024101:Mitochondrial Proteins; D016877:Oxidants; D006861:Hydrogen Peroxide; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex