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Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev 2004 Nov 15;18(22):2785-97

Date

11/03/2004

Pubmed ID

15520274

Pubmed Central ID

PMC528898

DOI

10.1101/gad.1247904

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.

Author List

Fannjiang Y, Cheng WC, Lee SJ, Qi B, Pevsner J, McCaffery JM, Hill RB, BasaƱez G, Hardwick JM

Author

Ronald Blake Hill PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Apoptosis
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
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1