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bioRxiv · 10.64898/2026.10.05.756849

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

Xiao, T.·Styler, B. S.·Ünal, E.
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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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Xiao, T., Styler, B. S., Ünal, E.. 2026-10-07. Vac8-driven vacuolar remodeling primes mega-autophagy and safeguardsgamete developmental competence. https://doi.org/10.64898/2026.10.05.756849

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