Gametogenesis: Exploring an Endogenous Rejuvenation Program to Understand Cellular Aging and Quality Control

Abstract

Gametogenesis is a conserved developmental program whereby a diploid progenitor cell differentiates into haploid gametes, the precursors for sexually reproducing organisms. In addition to ploidy reduction and extensive organelle remodeling, gametogenesis naturally rejuvenates the ensuing gametes, leading to resetting of life span. Excitingly, ectopic expression of the gametogenesis-specific transcription factor Ndt80 is sufficient to extend life span in mitotically dividing budding yeast, suggesting that meiotic rejuvenation pathways can be repurposed outside of their natural context. In this review, we highlight recent studies of gametogenesis that provide emerging insight into natural quality control, organelle remodeling, and rejuvenation strategies that exist within a cell. These include selective inheritance, programmed degradation, and de novo synthesis, all of which are governed by the meiotic gene expression program entailing many forms of noncanonical gene regulation. Finally, we highlight critical questions that remain in the field and provide perspective on the implications of gametogenesis research on human health span. Expected final online publication date for the Annual Review of Genetics, Volume 56 is November 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Meiotic Cytokinesis in Saccharomyces cerevisiae: Spores That Just Need Closure

“…Closure of the prospore membrane leads to cellularization and is the cytokinetic event of meiosis, as this event separates the nuclei of the daughter cells from the mother cell cytoplasm and also captures some cytoplasmic components from the mother cell. Aging-related factors are kept in the mother cell and segregated away from the spore during sporulation, creating robust gametes (reviewed in [24]). The prospore membrane is important for spore morphogenesis, as the spore wall is deposited within the lumen of the double lipid bilayer of the prospore membrane.…”

Remodeling of the secretory pathway is coordinated withde novomembrane formation in budding yeast gametogenesis

“…More recently, the molecular mechanisms responsible for the morphology of the ER during meiosis and for the distribution of the mitochondria have also been elucidated 21,22 . Although these organellar remodeling processes are shown to be a system to exclude unnecessary organelles rather than an active transport machinery toward the gametes, they are crucial to the cell, as it is inherently linked to cell rejuvenation by eliminating age-related factors from the gametes 2,23 . In this case, the PSM provides a barrier between age-related factors such as damaged organelles and essential organelles including nucleus to be inherited by the next generation.…”

“…In meiosis II, a newly generated membrane, the prospore membrane (PSM), is formed at the cytoplasmic surface of the spindle pole body (SPB) embedded in the nuclear membrane, and the haploid set of chromosomes in the nucleus is engulfed by the growing PSM, along with organelles and cytosol 1 . This process is triggered by starvation, accompanied by a massive remodeling in the mother cell, is carried out through the strict control of transcription and translation, and depends on membrane traffic 1,2 .…”