title: Differential expression and glycative damage affect specific mitochondrial proteins with aging in rat liver.
abstract: Aging is accompanied by the gradual deterioration of cell functions. Particularly, mitochondrial dysfunction, associated with an accumulation of damaged proteins, is of key importance due to the central role of these organelles in cellular metabolism. However, the detailed molecular mechanisms involved in such impairment have not been completely elucidated. In the present study, proteomic analyses looking at both changes at the expression level as well as to glycative modifications of the mitochondrial proteome were performed. Two-dimensional difference gel electrophoresis analysis revealed 16 differentially expressed proteins with aging. Thirteen exhibited a decreased expression and are crucial enzymes related to OXPHOS chain complex I/V components, TCA cycle or fatty acid β-oxidation reaction. On the other hand, 2 enzymes involved in fatty acid β-oxidation cycle were increased in aged mitochondria. Immunodetection and further identification of glycated proteins disclosed a set of advanced glycation end product-modified proteins, including 6 enzymes involved in the fatty acid β-oxidation process, and 2 enzymes of the TCA/urea cycles. A crucial antioxidant enzyme, catalase, was among the most strongly glycated proteins. In addition, several AGE-damaged enzymes (aldehyde dehydrogenase 2, medium chain acyl-CoA dehydrogenase and 3-ketoacyl-CoA dehydrogenase) exhibited a decreased activity with age. Taken together, these data suggest that liver mitochondria in old rats suffer from a decline in their capacity for energy production, due to (i) decreased expression of OXPHOS complex I/V components and (ii) glycative damage to key fatty acid β-oxidation and TCA/urea cycle enzymes.
authors.affiliation: Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UFR SDV, 75205 Paris Cedex 13, France; Laboratoire de Biologie Cellulaire du Vieillissement, UR4-UPMC, IFR 83, Université Pierre et Marie Curie-Paris 6, 75252 Paris Cedex 05, France. Electronic address: Bakala@univ-paris-diderot.fr.
authors.forename: Hilaire
authors.initials: H
authors.lastname: Bakala
authors.forename: Romain
authors.initials: R
authors.lastname: Ladouce
authors.forename: Martin A
authors.initials: MA
authors.lastname: Baraibar
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D024101:Mitochondrial Proteins
keywords: 2D-DIGE; 2D-GE; 3-ketoacyl-CoA thiolase; AGE; ALDH2; Aging; Glycation; MCAD; MS; MTP; Mitochondria; OXPHOS; PPAR-γ; Peroxisomal proliferators-activated receptor gamma; Protein expression; Proteomics; THIM; advanced glycation endproduct; aldehyde dehydrogenase-2; mass spectrometry; medium chain acyl-CoA dehydrogenase; mitochondrial trifunctional protein; oxidative phosphorylation; two-dimensional difference gel electrophoresis; two-dimensional gel electrophoresis