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PreprintCC BY-NCbioRxiv

Vac8-driven vacuolar remodeling primes mega-autophagy and safeguardsgamete developmental competence

Abstract

During gametogenesis, organelle remodeling is coordinated alongside chromosome segregation to ensure gamete quality. In Saccharomyces cerevisiae, the precursor-cell vacuole permeabilizes following completion of meiotic divisions, releasing hydrolytic enzymes that degrade cellular material excluded from gametes. The regulation and biological significance of this developmentally-programmed process, termed mega-autophagy, remain poorly understood. Here we identify the conserved armadillo repeat-containing protein Vac8 as a key regulator of mega-autophagy. The presence of Vac8 during meiosis is required for timely execution of mega-autophagy. Specifically, during anaphase II, precursor-cell vacuoles undergo Vac8-dependent fusion to form fewer, larger structures. Deleting VAC8 disrupts this remodeling and impairs subsequent vacuolar permeabilization, establishing meiotic vacuolar fusion as a prerequisite for mega-autophagy. Defective mega-autophagy compromises the ability of gametes to exit dormancy and proliferate upon nutrient repletion. Together, these findings reveal that Vac8-mediated vacuolar remodeling during meiosis primes a post-meiotic quality-control mechanism that safeguards gamete developmental competence.

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BibTeX
@misc{xiao2026vac8driven,
  title = {{Vac8-driven vacuolar remodeling primes mega-autophagy and safeguardsgamete developmental competence}},
  author = {T. Xiao and B. S. Styler and E. Ünal},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.05.756849},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756849v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Vac8-driven vacuolar remodeling primes mega-autophagy and safeguardsgamete developmental competence
AU  - T. Xiao
AU  - B. S. Styler
AU  - E. Ünal
PY  - 2026
DA  - 2026/10/05
PB  - bioRxiv
DO  - 10.64898/2026.10.05.756849
UR  - https://www.biorxiv.org/content/10.64898/2026.10.05.756849v1
AB  - During gametogenesis, organelle remodeling is coordinated alongside chromosome segregation to ensure gamete quality. In Saccharomyces cerevisiae, the precursor-cell vacuole permeabilizes following completion of meiotic divisions, releasing hydrolytic enzymes that degrade cellular material excluded from gametes. The regulation and biological significance of this developmentally-programmed process, termed mega-autophagy, remain poorly understood. Here we identify the conserved armadillo repeat-containing protein Vac8 as a key regulator of mega-autophagy. The presence of Vac8 during meiosis is required for timely execution of mega-autophagy. Specifically, during anaphase II, precursor-cell vacuoles undergo Vac8-dependent fusion to form fewer, larger structures. Deleting VAC8 disrupts this remodeling and impairs subsequent vacuolar permeabilization, establishing meiotic vacuolar fusion as a prerequisite for mega-autophagy. Defective mega-autophagy compromises the ability of gametes to exit dormancy and proliferate upon nutrient repletion. Together, these findings reveal that Vac8-mediated vacuolar remodeling during meiosis primes a post-meiotic quality-control mechanism that safeguards gamete developmental competence.
ER  -