Format

Send to

Choose Destination
See comment in PubMed Commons below
Oxid Med Cell Longev. 2013;2013:678473. doi: 10.1155/2013/678473. Epub 2013 Sep 5.

Lack of HXK2 induces localization of active Ras in mitochondria and triggers apoptosis in the yeast Saccharomyces cerevisiae.

Author information

1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza Della Scienza 2, 20126 Milan, Italy ; SysBio Centre of Systems Biology, Piazza Della Scienza 2, 20126 Milan, Italy.

Abstract

We recently showed that activated Ras proteins are localized to the plasma membrane and in the nucleus in wild-type cells growing exponentially on glucose, while in the hxk2Δ strain they accumulated mainly in mitochondria. An aberrant accumulation of activated Ras in these organelles was previously reported and correlated to mitochondrial dysfunction, accumulation of ROS, and cell death. Here we show that addition of acetic acid to wild-type cells results in a rapid recruitment of Ras-GTP from the nucleus and the plasma membrane to the mitochondria, providing a further proof that Ras proteins might be involved in programmed cell death. Moreover, we show that Hxk2 protects against apoptosis in S. cerevisiae. In particular, cells lacking HXK2 and showing a constitutive accumulation of activated Ras at the mitochondria are more sensitive to acetic-acid-induced programmed cell death compared to the wild type strain. Indeed, deletion of HXK2 causes an increase of apoptotic cells with several morphological and biochemical changes that are typical of apoptosis, including DNA fragmentation, externalization of phosphatidylserine, and ROS production. Finally, our results suggest that apoptosis induced by lack of Hxk2 may not require the activation of Yca1, the metacaspase homologue identified in yeast.

PMID:
24089630
PMCID:
PMC3780702
DOI:
10.1155/2013/678473
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Hindawi Publishing Corporation Icon for PubMed Central
    Loading ...
    Support Center