Journal article
Mitochondrial tolerance to stress impaired in failing heart
Journal of molecular and cellular cardiology, Vol.35(9), pp.1161-1166
2003
DOI: 10.1016/S0022-2828(03)00204-9
PMID: 12967639
Abstract
Mitochondrial integrity is critical in the maintenance of bioenergetic homeostasis of the myocardium, with oxidative or metabolic challenge to mitochondria precipitating cell injury. In heart failure, where cardiac cells are exposed to elevated stress, mitochondrial vulnerability could contribute to the disease state. However, the mitochondrial response to stress is yet to be established in heart failure. Here, mitochondrial function and structure was evaluated prior and following stress using a transgenic (TG) model of heart failure, generated by cardiac overexpression of the cytokine TNFα. Compared to the wild type, mitochondria from TG failing hearts demonstrated impaired oxidative phosphorylation, mitochondrial DNA damage, reduced mitochondrial creatine kinase activity, abnormal calcium handling, and altered ultrastructure. Under anoxia/reoxygenation or calcium stress, mitochondria from failing hearts suffered exacerbated energetic failure with pronounced cytochrome
c release. Thus, mitochondria from TNFα-TG failing hearts demonstrate structural and functional abnormalities, with reduced tolerance to stress manifested by impaired bioenergetics and increased susceptibility to injury. This abnormal vulnerability to stress underscores the impact of mitochondrial dysfunction in the pathobiology of heart failure.
Details
- Title: Subtitle
- Mitochondrial tolerance to stress impaired in failing heart
- Creators
- Cevher Ozcan - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Guggenheim-7F, Rochester, MN 55905, USAMartin Bienengraeber - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Guggenheim-7F, Rochester, MN 55905, USADenice M Hodgson - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Guggenheim-7F, Rochester, MN 55905, USADouglas L Mann - Winters Center for Heart Failure Research, Baylor College of Medicine and Houston Veterans Administration Medical Center, Houston, TX 77030, USAAndre Terzic - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Guggenheim-7F, Rochester, MN 55905, USA
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.35(9), pp.1161-1166
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/S0022-2828(03)00204-9
- PMID
- 12967639
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Language
- English
- Date published
- 2003
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094622802771
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