title: Protein carbonylation and adipocyte mitochondrial function.
abstract: Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte.
authors: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis Minnesota 55455, USA.
authors: Jessica M
authors: JM
authors: Curtis
authors: Wendy S
authors: WS
authors: Hahn
authors: Matthew D
authors: MD
authors: Stone
authors: Jacob J
authors: JJ
authors: Inda
authors: David J
authors: DJ
authors: Droullard
authors: Jovan P
authors: JP
authors: Kuzmicic
authors: Margaret A
authors: MA
authors: Donoghue
authors: Eric K
authors: EK
authors: Long
authors: Anibal G
authors: AG
authors: Armien
authors: Sergio
authors: S
authors: Lavandero
authors: Edgar
authors: E
authors: Arriaga
authors: Timothy J
authors: TJ
authors: Griffin
authors: David A
authors: DA
authors: Bernlohr
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D020868:Gene Silencing; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D050050:Protein Carbonylation / Q000502:physiology*
chemical_list: D024101:Mitochondrial Proteins