Publication Date:
2022-10-27
Description:
© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Stolp, Z. D., Kulkarni, M., Liu, Y., Zhu, C., Jalisi, A., Lin, S., Casadevall, A., Cunningham, K. W., Pineda, F. J., Teng, X., & Hardwick, J. M. Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization. Cell Reports, 39(2), (2022): 110647, https://doi.org/10.1016/j.celrep.2022.110647.
Description:
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.
Description:
Funding sources: National Institutes of Health, United States grants AI144373 and NS127076 (J.M.H.), AI115016 and AI153414 (K.W.C.), and AI052733, AI152078, and HL059842 (A.C.); National Natural Science Foundation of China 31970550; and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (X.T.).
Keywords:
Yeast
;
Programmed cell death
;
Vesicle trafficking
;
AP-3
;
Vacuole
;
Cryptococcus
;
Yck3
;
Regulated cell death
;
Lysosome
;
Vacuolar membrane permeabilization
Repository Name:
Woods Hole Open Access Server
Type:
Article
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