Mitochondrial Dysfunction Increases Oxidative Stress and Decreases Chronological Life Span in Fission Yeast

PLoS One. 2008 Jul 30;3(7):e2842. doi: 10.1371/journal.pone.0002842.

Abstract

Background: Oxidative stress is a probable cause of aging and associated diseases. Reactive oxygen species (ROS) originate mainly from endogenous sources, namely the mitochondria.

Methodology/principal findings: We analyzed the effect of aerobic metabolism on oxidative damage in Schizosaccharomyces pombe by global mapping of those genes that are required for growth on both respiratory-proficient media and hydrogen-peroxide-containing fermentable media. Out of a collection of approximately 2700 haploid yeast deletion mutants, 51 were sensitive to both conditions and 19 of these were related to mitochondrial function. Twelve deletion mutants lacked components of the electron transport chain. The growth defects of these mutants can be alleviated by the addition of antioxidants, which points to intrinsic oxidative stress as the origin of the phenotypes observed. These respiration-deficient mutants display elevated steady-state levels of ROS, probably due to enhanced electron leakage from their defective transport chains, which compromises the viability of chronologically-aged cells.

Conclusion/significance: Individual mitochondrial dysfunctions have often been described as the cause of diseases or aging, and our global characterization emphasizes the primacy of oxidative stress in the etiology of such processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / chemistry
  • Cell Respiration
  • DNA, Mitochondrial
  • Electrons
  • Gene Deletion
  • Hydrogen Peroxide / pharmacology
  • Mitochondria / pathology*
  • Models, Biological
  • Mutation
  • Oxidative Stress*
  • Oxygen / chemistry
  • Oxygen Consumption
  • Reactive Oxygen Species
  • Schizosaccharomyces / physiology*
  • Time Factors

Substances

  • DNA, Mitochondrial
  • Reactive Oxygen Species
  • Carbon
  • Hydrogen Peroxide
  • Oxygen