The ESCRT-III complex is required for nuclear pore complex sequestration and regulates gamete replicative lifespan in budding yeast meiosis

Cellular aging occurs as a cell loses its ability to maintain homeostasis. Aging cells eliminate damaged cellular compartments and other senescence factors via self-renewal. The mechanism that regulates cellular rejuvenation remains to be further elucidated. Using budding yeast gametogenesis as a model, we show here that the endosomal sorting complex required for transport (ESCRT) III regulates nuclear envelope organization. During gametogenesis, the nuclear pore complex (NPC) and other senescence factors are sequestered away from the prospore nuclei. We show that the LEM-domain protein Heh1 (Src1) facilitates the nuclear recruitment of ESCRT-III, which is required for meiotic NPC sequestration and nuclear envelope remodeling. Furthermore, ESCRT-III-mediated nuclear reorganization appears to be critical for gamete rejuvenation, as hindering this process curtails either directly or indirectly the replicative lifespan in gametes. Our findings demonstrate the importance of ESCRT-III in nuclear envelope remodeling and its potential role in eliminating senescence factors during gametogenesis.细胞衰老（cellular aging）发生于细胞丧失维持稳态（homeostasis）的能力之际。衰老细胞可通过自我更新清除受损的细胞区室及其他衰老因子。目前，调控细胞复壮（cellular rejuvenation）的机制仍有待进一步阐明。本研究以出芽酵母配子发生（budding yeast gametogenesis）为模型，证实转运所需的内体分选复合物III（endosomal sorting complex required for transport III, ESCRT III）可调控核被膜组织。在配子发生过程中，核孔复合物（nuclear pore complex, NPC）及其他衰老因子会被隔离至前孢子核之外。研究发现，LEM结构域蛋白（LEM-domain protein）Heh1（Src1）可促进ESCRT-III向细胞核的招募，而这一过程是减数分裂期核孔复合物隔离与核被膜重塑所必需的。此外，ESCRT-III介导的细胞核重组似乎对配子复壮至关重要：阻碍该过程会直接或间接缩短配子的复制寿命（replicative lifespan）。本研究结果证实了ESCRT-III在核被膜重塑中的重要作用，以及其在配子发生过程中清除衰老因子的潜在功能。