Scholars@Duke publication: GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels.

GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels.

Publication , Journal Article

Sato, PY; Chuprun, JK; Ibetti, J; Cannavo, A; Drosatos, K; Elrod, JW; Koch, WJ

Published in: J Mol Cell Cardiol

December 2015

The G protein-coupled receptor kinase-2 (GRK2) is upregulated in the injured heart and contributes to heart failure pathogenesis. GRK2 was recently shown to associate with mitochondria but its functional impact in myocytes due to this localization is unclear. This study was undertaken to determine the effect of elevated GRK2 on mitochondrial respiration in cardiomyocytes. Sub-fractionation of purified cardiac mitochondria revealed that basally GRK2 is found in multiple compartments. Overexpression of GRK2 in mouse cardiomyocytes resulted in an increased amount of mitochondrial-based superoxide. Inhibition of GRK2 increased oxygen consumption rates and ATP production. Moreover, fatty acid oxidation was found to be significantly impaired when GRK2 was elevated and was dependent on the catalytic activity and mitochondrial localization of this kinase. Our study shows that independent of cardiac injury, GRK2 is localized in the mitochondria and its kinase activity negatively impacts the function of this organelle by increasing superoxide levels and altering substrate utilization for energy production.

Duke Scholars

Author Walter J. Koch Surgery, Cardiovascular and Thoracic Surgery

Published In

J Mol Cell Cardiol

DOI

10.1016/j.yjmcc.2015.10.002

EISSN

1095-8584

Publication Date

December 2015

Volume

Issue

Pt B

Start / End Page

360 / 364

Location

England

Related Subject Headings

Superoxides
Stress, Physiological
Oxygen Consumption
Myocytes, Cardiac
Mitochondria, Heart
Mice, Transgenic
G-Protein-Coupled Receptor Kinase 2
Fatty Acids
Cell Respiration
Cardiovascular System & Hematology

Citation

APA

Chicago

ICMJE

MLA

NLM

Sato, P. Y., Chuprun, J. K., Ibetti, J., Cannavo, A., Drosatos, K., Elrod, J. W., & Koch, W. J. (2015). GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels. J Mol Cell Cardiol, 89(Pt B), 360–364. https://doi.org/10.1016/j.yjmcc.2015.10.002

Sato, Priscila Y., J Kurt Chuprun, Jessica Ibetti, Alessandro Cannavo, Konstantinos Drosatos, John W. Elrod, and Walter J. Koch. “GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels.” J Mol Cell Cardiol 89, no. Pt B (December 2015): 360–64. https://doi.org/10.1016/j.yjmcc.2015.10.002.

Sato PY, Chuprun JK, Ibetti J, Cannavo A, Drosatos K, Elrod JW, et al. GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels. J Mol Cell Cardiol. 2015 Dec;89(Pt B):360–4.

Sato, Priscila Y., et al. “GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels.” J Mol Cell Cardiol, vol. 89, no. Pt B, Dec. 2015, pp. 360–64. Pubmed, doi:10.1016/j.yjmcc.2015.10.002.

Sato PY, Chuprun JK, Ibetti J, Cannavo A, Drosatos K, Elrod JW, Koch WJ. GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels. J Mol Cell Cardiol. 2015 Dec;89(Pt B):360–364.