Protein carbonylation and adipocyte mitochondrial function

Jessica M. Curtis, Wendy S. Hahn, Matthew D. Stone, Jacob J. Inda, David J. Droullard, Jovan P. Kuzmicic, Margaret A. Donoghue, Eric K. Long, Anibal G. Armien, Sergio Lavandero, Edgar Arriaga, Timothy J. Griffin, David A. Bernlohr

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)32967-32980
Number of pages14
JournalJournal of Biological Chemistry
Volume287
Issue number39
DOIs
StatePublished - Sep 21 2012

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Protein Carbonylation
Carbonylation
Adipocytes
Phosphate Transport Proteins
NADH Dehydrogenase
Valine-tRNA Ligase
Respiration
3T3-L1 Cells
Proteins
Mitochondrial Proteins
Mitochondrial Membranes
Histidine
Superoxides
Membrane Potentials
Proteomics
Energy Metabolism
Lipid Peroxidation
Lysine
Cysteine
Insulin Resistance

Cite this

Curtis, J. M., Hahn, W. S., Stone, M. D., Inda, J. J., Droullard, D. J., Kuzmicic, J. P., ... Bernlohr, D. A. (2012). Protein carbonylation and adipocyte mitochondrial function. Journal of Biological Chemistry, 287(39), 32967-32980. https://doi.org/10.1074/jbc.M112.400663

Protein carbonylation and adipocyte mitochondrial function. / Curtis, Jessica M.; Hahn, Wendy S.; Stone, Matthew D.; Inda, Jacob J.; Droullard, David J.; Kuzmicic, Jovan P.; Donoghue, Margaret A.; Long, Eric K.; Armien, Anibal G.; Lavandero, Sergio; Arriaga, Edgar; Griffin, Timothy J.; Bernlohr, David A.

In: Journal of Biological Chemistry, Vol. 287, No. 39, 21.09.2012, p. 32967-32980.

Research output: Contribution to journalArticle

Curtis, JM, Hahn, WS, Stone, MD, Inda, JJ, Droullard, DJ, Kuzmicic, JP, Donoghue, MA, Long, EK, Armien, AG, Lavandero, S, Arriaga, E, Griffin, TJ & Bernlohr, DA 2012, 'Protein carbonylation and adipocyte mitochondrial function', Journal of Biological Chemistry, vol. 287, no. 39, pp. 32967-32980. https://doi.org/10.1074/jbc.M112.400663
Curtis JM, Hahn WS, Stone MD, Inda JJ, Droullard DJ, Kuzmicic JP et al. Protein carbonylation and adipocyte mitochondrial function. Journal of Biological Chemistry. 2012 Sep 21;287(39):32967-32980. https://doi.org/10.1074/jbc.M112.400663
Curtis, Jessica M. ; Hahn, Wendy S. ; Stone, Matthew D. ; Inda, Jacob J. ; Droullard, David J. ; Kuzmicic, Jovan P. ; Donoghue, Margaret A. ; Long, Eric K. ; Armien, Anibal G. ; Lavandero, Sergio ; Arriaga, Edgar ; Griffin, Timothy J. ; Bernlohr, David A. / Protein carbonylation and adipocyte mitochondrial function. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 39. pp. 32967-32980.
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