Mitochondrial tolerance to stress impaired in failing heart

Cevher Ozcan, Martin Bienengraeber, Denice M. Hodgson, Douglas L. Mann, Andre Terzic

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1161-1166
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume35
Issue number9
DOIs
StatePublished - Sep 1 2003

Fingerprint

Heart Failure
Mitochondria
Energy Metabolism
Mitochondrial Form Creatine Kinase
Calcium
Heart Mitochondria
Oxidative Phosphorylation
Wounds and Injuries
Cytochromes c
Mitochondrial DNA
DNA Damage
Myocardium
Homeostasis
Maintenance
Cytokines

Keywords

  • Calcium
  • Energy metabolism
  • Heart failure
  • Mitochondria
  • Oxidative stress
  • TNFα

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Mitochondrial tolerance to stress impaired in failing heart. / Ozcan, Cevher; Bienengraeber, Martin; Hodgson, Denice M.; Mann, Douglas L.; Terzic, Andre.

In: Journal of Molecular and Cellular Cardiology, Vol. 35, No. 9, 01.09.2003, p. 1161-1166.

Research output: Contribution to journalArticle

Ozcan, Cevher ; Bienengraeber, Martin ; Hodgson, Denice M. ; Mann, Douglas L. ; Terzic, Andre. / Mitochondrial tolerance to stress impaired in failing heart. In: Journal of Molecular and Cellular Cardiology. 2003 ; Vol. 35, No. 9. pp. 1161-1166.
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