Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes

Kashyap B. Choksi, Jonathan E. Nuss, William H. Boylston, Jeffrey P. Rabek, John Papaconstantinou

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Mitochondrial dysfunction generates reactive oxygen species (ROS) which damage essential macromolecules. Oxidative modification of proteins, DNA, and lipids has been implicated as a major causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain complexes I and III are the principal sites of ROS production, and oxidative modifications to the complex subunits inhibit their in vitro activity. Therefore, we hypothesize that mitochondrial complex subunits may be primary targets for oxidative damage by ROS which may impair normal complex activity by altering their structure/function leading to mitochondrial dysfunction associated with aging. This study of kidney mitochondria from young, middle-aged, and old mice reveals that there are functional decreases in complexes I, II, IV, and V between aged compared to young kidney mitochondria and these functional declines directly correlate with increased oxidative modification to particular complex subunits. We postulate that the electron leakage from 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 seen in aged mouse kidney. In conclusion, increasing mitochondrial dysfunction may play a key role in the age-associated decline in tissue function.

Original languageEnglish (US)
Pages (from-to)1423-1438
Number of pages16
JournalFree Radical Biology and Medicine
Volume43
Issue number10
DOIs
StatePublished - Nov 15 2007

Keywords

  • 4-Hydroxynonenal
  • Aging
  • Malondialdehyde
  • Mitochondrial dysfunction
  • Nitration
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes'. Together they form a unique fingerprint.

  • Cite this