Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev 2004 Nov 15;18(22):2785-97
Date
11/03/2004Pubmed ID
15520274Pubmed Central ID
PMC528898DOI
10.1101/gad.1247904Scopus ID
2-s2.0-8644284924 (requires institutional sign-in at Scopus site) 270 CitationsAbstract
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.
Author List
Fannjiang Y, Cheng WC, Lee SJ, Qi B, Pevsner J, McCaffery JM, Hill RB, Basañez G, Hardwick JMMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingApoptosis
Carrier Proteins
Cysteine Endopeptidases
GTP Phosphohydrolases
Humans
Membranes, Artificial
Mitochondria
Mitochondrial Proteins
Nerve Tissue Proteins
Phospholipids
Proto-Oncogene Proteins c-bcl-2
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
bcl-X Protein
