Meiotic cellular rejuvenation is coupled to nuclear remodeling in budding yeast

Abstract

Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors – including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material – are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and aged cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly, de novo generation of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.

Nuclear envelope-vacuole contacts mitigate nuclear pore complex assembly stress

“…NPC assembly and nuclear transport play essential roles in modulating yeast replicative life span (Lord et al, 2015Rempel et al, 2019;King et al, 2019), and disrupted NPC function is associated with aging and neurological disorders in metazoans (D'Angelo et al, 2009;Toyama et al, 2013;Cruz and Cleveland, 2016). Given their impact on promoting proper NPC formation and viability in mutants with disrupted NPC assembly, it will be important to define how NE-vacuole interactions regulate the replicative aging process and potentially other stress conditions.…”

A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage

“…Oocytes can also eliminate defective organelles or age-related molecular damage. For example, in mice, mitochondria containing defective DNA are eliminated during oogenesis ( Fan et al, 2008 ), and in yeast, nuclear senescence factors and protein aggregates are extruded during meiosis ( King et al, 2019 ; Unal et al, 2011 ). Mechanisms likely exist to counteract protein aggregation in Drosophila as well: relative to the soma, the eggs of Drosophila exhibit enhanced proteasome activity and resistance to protein aggregation ( Fredriksson et al, 2012 ).…”

A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage

“…Oocytes can also eliminate defective organelles or age-related molecular damage. For example, in mice, mitochondria containing defective DNA are eliminated during oogenesis (Fan et al, 2008), and in yeast, nuclear senescence factors and protein aggregates are extruded during meiosis (King et al, 2019; Ünal et al, 2011). Mechanisms likely exist to counteract protein aggregation in Drosophila as well: relative to the soma, the eggs of Drosophila exhibit enhanced proteasome activity and resistance to protein aggregation (Fredriksson et al, 2012).…”