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

Authors

Xiao, T., Styler, B. S., Ünal, E.

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Oct 2026.

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