Vacuolar fragmentation promotes fluxes of microautophagy and micronucleophagy but not of macroautophagy

Abstract

Vacuoles and lysosomes are organelles involved in the degradation of cytoplasmic proteins and organelles. Vacuolar morphology is dynamically regulated by fission and fusion in budding yeast. Vacuolar fusion is elicited in nutrient-depleted conditions and mediated by inactivation of target of rapamycin complex 1 (TORC1) protein kinase. However, it is unknown whether and how vacuolar morphology affects macroautophagy and microautophagy, which are induced by nutrient starvation and TORC1 inactivation. Here, we developed a system to control vacuolar fission in budding yeast. Vacuolar fragmentation promoted microautophagy but not macroautophagy. Vacuolar fragmentation caused multiple nucleus-vacuole junctions. Multiple vacuoles caused by vacuolar fragmentation also improved micronucleophagy (microautophagic degradation of a portion of the nucleus). However, vacuolar morphology did not impact nucleolar remodeling, condensation of the rDNA (rRNA gene) region, or separation of ribosomal DNA from nucleolar proteins, which is evoked by TORC1 inactivation. Thus, this study provides insights into the impacts of vacuolar/lysosomal morphology on macroautophagy and microautophagy.

Keywords: Chromosome condensation; Macroautophagy; Microautophagy; Micronucleophagy; Ribosomal DNA (rDNA); Vacuole.