Abstract
Unicellular eukaryotes have been suggested as undergoing self-inflicted destruction. However, molecular details are sparse compared with the mechanisms of programmed/regulated cell death known for human cells and animal models. Here, we report a molecular cell death pathway in Saccharomyces cerevisiae leading to vacuole/lysosome membrane permeabilization. Following a transient cell death stimulus, yeast cells die slowly over several hours, consistent with an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 complex, a vesicle trafficking adapter known to transport and install newly synthesized proteins on the vacuole/lysosome membrane. To promote cell death, AP-3 requires its Arf1-GTPase-dependent vesicle trafficking function and the kinase Yck3, which is selectively transported to the vacuole membrane by AP-3. Video microscopy revealed a sequence of events where vacuole permeability precedes the loss of plasma membrane integrity. AP-3-dependent death appears to be conserved in the human pathogenic yeast Cryptococcus neoformans.
Original language | English (US) |
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Article number | 110647 |
Journal | Cell Reports |
Volume | 39 |
Issue number | 2 |
DOIs | |
State | Published - Apr 12 2022 |
Keywords
- AP-3
- CP: Cell biology
- Yck3
- cryptococcus
- lysosome
- programmed cell death
- regulated cell death
- vacuolar membrane permeabilization
- vacuole
- vesicle trafficking
- yeast
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology