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Mitochondrial fission proteins regulate programmed cell death in yeast

Open access
Fannjiang, Yihru, Cheng, Wen-Chih, Lee, Sarah J., Qi, Bing, Pevsner, Jonathan, McCaffery, J. Michael, Hill, R. Blake, Basañez, Gorka, Hardwick, J. Marie·2004·Genes & Development

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-x L . 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.

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Metadata

Authors
Fannjiang, Y., Cheng, W.-C., Lee, S. J., Qi, B., Pevsner, J., McCaffery, J. M., Hill, R. B., Basañez, G., & Hardwick, J. M.
Venue
Genes & Development
Published
2004-11-01
Volume
18
Issue
22
Pages
2785-2797
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2126274369
Cited by
304
References
8
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: Mitochondrial fission proteins regulate programmed cell death in yeast. https://app.cochat.ai/papers/10.1101/gad.1247904
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Fannjiang, Y., Cheng, W.-C., Lee, S. J., Qi, B., Pevsner, J., McCaffery, J. M., Hill, R. B., Basañez, G., & Hardwick, J. M. (2004). Mitochondrial fission proteins regulate programmed cell death in yeast. Genes & Development. https://doi.org/10.1101/gad.1247904

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