Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Metab. 2013 Aug 6;18(2):279-86. doi: 10.1016/j.cmet.2013.07.005.

Loss of cytochrome c oxidase promotes RAS-dependent ROS production from the ER resident NADPH oxidase, Yno1p, in yeast.

Author information

1
School of Biosciences, University of Kent, Canterbury, UK.

Abstract

Many disease states, including the aging process, are associated with the accumulation of mitochondria harboring respiratory dysfunction. Mitochondrial dysfunction is often accompanied by increased ROS levels that can contribute to cellular dysfunction and disease etiology. Here we use the model eukaryote S. cerevisiae to investigate whether reduced cytochrome c oxidase (COX) activity, commonly reported in aging organisms and associated with neurodegenerative disorders, leads to ROS production from mitochondria. We provide evidence that although reduced COX complex activity correlates with ROS accumulation, mitochondria are not the major production center. Instead we show that COX-deficient mitochondria activate Ras upon their outer membrane that establishes a pro-ROS accumulation environment by suppressing antioxidant defenses and the ERAD-mediated turnover of the ER-localized NADPH oxidase Yno1p. Our data suggest that dysfunctional mitochondria can serve as a signaling platform to promote the loss of redox homeostasis, ROS accumulation, and accelerate aging in yeast.

PMID:
23931758
DOI:
10.1016/j.cmet.2013.07.005
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center