Mitochondria play a critical role in mediating the cellular response to oxidants formed during acute and chronic cardiac dysfunction. It is widely assumed that, as cells are subjected to stress, mitochondria are capable of drawing upon a ‘reserve capacity’ which is available to serve the increased energy demands for maintenance of organ function, cellular repair or detoxification of reactive species. This hypothesis further implies that impairment or depletion of this putative reserve capacity ultimately leads to excessive protein damage and cell death. However, it has been difficult to fully evaluate this hypothesis since much of our information about the response of the mitochondrion to oxidative stress derives from studies on mitochondria isolated from their cellular context. Therefore the goal of the present study was to determine whether ‘bioenergetic reserve capacity’ does indeed exist in the intact myocyte and whether it is utilized in response to stress induced by the pathologically relevant reactive lipid species HNE (4-hydroxynonenal). We found that intact rat neonatal ventricular myocytes exhibit a substantial bioenergetic reserve capacity under basal conditions; however, on exposure to pathologically relevant concentrations of HNE, oxygen consumption was increased until this reserve capacity was depleted. Exhaustion of the reserve capacity by HNE treatment resulted in inhibition of respiration concomitant with protein modification and cell death. These data suggest that oxidized lipids could contribute to myocyte injury by decreasing the bioenergetic reserve capacity. Furthermore, these studies demonstrate the utility of measuring the bioenergetic reserve capacity for assessing or predicting the response of cells to stress.
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November 2009
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Research Article|
October 23 2009
Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal
Bradford G. Hill;
Bradford G. Hill
1
*Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0022, U.S.A.
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Brian P. Dranka;
Brian P. Dranka
1
*Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0022, U.S.A.
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Luyun Zou;
Luyun Zou
†Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0022, U.S.A.
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John C. Chatham;
John C. Chatham
†Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0022, U.S.A.
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Victor M. Darley-Usmar
Victor M. Darley-Usmar
2
*Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0022, U.S.A.
2To whom correspondence should be addressed (email darley@uab.edu).
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Biochem J (2009) 424 (1): 99–107.
Article history
Received:
June 19 2009
Revision Received:
August 08 2009
Accepted:
September 10 2009
Accepted Manuscript online:
September 10 2009
Citation
Bradford G. Hill, Brian P. Dranka, Luyun Zou, John C. Chatham, Victor M. Darley-Usmar; Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J 15 November 2009; 424 (1): 99–107. doi: https://doi.org/10.1042/BJ20090934
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