Response to the increase of oxidative stress and mutation of mitochondrial DNA in aging

Yi Shing Ma, Shi Bei Wu, Wan Yu Lee, Ju San Cheng, Yau Huei Wei*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

In the aging process, mitochondrial function gradually declines with an increase of mutations in mitochondrial DNA (mtDNA) in tissue cells. Some of the aging-associated mtDNA mutations have been shown to result in not only inefficient generation of ATP but also increased production of reactive oxygen species (ROS) such as superoxide anions (O2{radical dot}-) and hydrogen peroxide (H2O2) in the mitochondria of aging tissues. Extensive studies have revealed that such an increase of oxidative stress is a contributory factor for alterations in the expression and activities of antioxidant enzymes and increased oxidative damage to DNA, RNA, proteins, and lipids in tissues and cultured cells from elderly subjects. Recently, we observed that gene expression of several proteins and enzymes related to iron metabolism is altered and that aconitase is extremely susceptible to oxidative damage in senescent skin fibroblasts and in cybrids harboring aging-associated A8344G mutation of mtDNA. Of great importance is the perturbation at the protein and activity levels of several enzymes containing iron-sulfur clusters in skin fibroblasts of elderly subjects. Taken together, these findings suggest that cellular response to oxidative stress and oxidative damage elicited by mitochondrial dysfunction and/or mtDNA mutations plays an important role in human aging.

Original languageEnglish
Pages (from-to)1021-1029
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number10
DOIs
StatePublished - 10 2009
Externally publishedYes

Keywords

  • Aging
  • Antioxidant enzyme
  • Iron-sulfur cluster
  • Mitochondrial DNA
  • Oxidative stress

Fingerprint

Dive into the research topics of 'Response to the increase of oxidative stress and mutation of mitochondrial DNA in aging'. Together they form a unique fingerprint.

Cite this