Protein Carbonylation and Adipocyte Mitochondrial Function

Curtis J.M.; Hahn W.S.; Stone M.D.; Inda J.J.; Droullard D.J.; Kuzmicic J.P.; Donoghue M.A.; Long E.K.; Armien A.G.; Lavandero S.; Arriaga E.; Griffin T.J.; Bernlohr D.A.

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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Más información

Título según WOS: Protein Carbonylation and Adipocyte Mitochondrial Function
Título según SCOPUS: Protein carbonylation and adipocyte mitochondrial function
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 287
Número: 39
Editorial: Elsevier
Fecha de publicación: 2012
Página de inicio: 32967
Página final: 32980
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-84866533507&partnerID=40&md5=d03885aec8b74a1abccff6409d72d3a1
DOI:

10.1074/jbc.M112.400663

Notas: ISI, SCOPUS