Mitochondrial fission proteins regulate programmed cell death in yeast

Yihru Fannjiang, Wen Chih Cheng, Sarah J. Lee, Bing Qi, Jonathan Pevsner, J. Michael McCaffery, R. Blake Hill, Gorka Basañez, J. Marie Hardwick

Research output: Contribution to journalArticlepeer-review

Abstract

The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1, Dnm1, promotes mitochondrial fragmentation/degradation and cell death following treatment with several death stimuli. Two Dnm1-interacting factors also regulate yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death, consistent with its role in mitochondrial fission. In contrast to its fission function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial fission and cysteine protease-dependent cell death in yeast. Furthermore, the ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function.

Original languageEnglish (US)
Pages (from-to)2785-2797
Number of pages13
JournalGenes and Development
Volume18
Issue number22
DOIs
StatePublished - Nov 15 2004

Keywords

  • Apoptosis
  • Autophagy
  • Bcl-xL
  • Dnm1
  • Drp1
  • Fis1
  • Mitochondria

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Mitochondrial fission proteins regulate programmed cell death in yeast'. Together they form a unique fingerprint.

Cite this