Mitochondrial fission proteins regulate programmed cell death in yeast

Genes Dev. 2004 Nov 15;18(22):2785-97. doi: 10.1101/gad.1247904. Epub 2004 Nov 1.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Apoptosis*
  • Carrier Proteins / metabolism
  • Cysteine Endopeptidases / metabolism
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Membranes, Artificial
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Nerve Tissue Proteins
  • Phospholipids / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • bcl-X Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • BCL2L1 protein, human
  • CRMP1 protein, human
  • Carrier Proteins
  • FIS1 protein, S cerevisiae
  • MDV1 protein, S cerevisiae
  • Membranes, Artificial
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • Phospholipids
  • Proto-Oncogene Proteins c-bcl-2
  • Saccharomyces cerevisiae Proteins
  • bcl-X Protein
  • Cysteine Endopeptidases
  • GTP Phosphohydrolases
  • DNM1 protein, S cerevisiae