Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes

Kashyap B. Choksi, John Papaconstantinou

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Mitochondrially generated ROS increase with age and are a major factor that damages proteins by oxidative modification. Accumulation of oxidatively damaged proteins has been implicated as a causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain (ETC) complexes I and III are the principle sites of ROS production, and oxidative modifications to their complex subunits inhibit their in vitro activity. We hypothesize that mitochondrial complex subunits may be primary targets for modification by ROS, which may impair normal complex activity. This study of heart mitochondria from young, middle-aged, and old mice reveals that there is an age-related decline in complex I and V activity that correlates with increased oxidative modification to their subunits. The data also show a specificity for modifications of the ETC complex subunits, i.e., several proteins have more than one type of adduct. We postulate that the electron leakage from ETC complexes causes specific damage to their subunits and increased ROS generation as oxidative damage accumulates, leading to further mitochondrial dysfunction, a cyclical process that underlies the progressive decline in physiologic function of the aged mouse heart.

Original languageEnglish (US)
Pages (from-to)1795-1805
Number of pages11
JournalFree Radical Biology and Medicine
Volume44
Issue number10
DOIs
StatePublished - May 15 2008

Fingerprint

Electron Transport
Electron Transport Complex I
Heart Mitochondria
Proteins
Mitochondria
Electron Transport Complex III
Age Factors
Electrons
Tissue

Keywords

  • 4-Hydroxynonenal
  • Aging
  • Carbonylation
  • Free radicals
  • Mitochondrial dysfunction
  • Nitration
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes. / Choksi, Kashyap B.; Papaconstantinou, John.

In: Free Radical Biology and Medicine, Vol. 44, No. 10, 15.05.2008, p. 1795-1805.

Research output: Contribution to journalArticle

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