Programmed cortical ER collapse drives selective ER degradation and inheritance in yeast meiosis

Abstract

The endoplasmic reticulum (ER) carries out essential and conserved cellular functions, which depend on the maintenance of its structure and subcellular distribution. Here, we report developmentally regulated changes in ER morphology and composition during budding yeast meiosis, a conserved differentiation program that gives rise to gametes. A subset of the cortical ER collapses away from the plasma membrane at anaphase II, thus separating into a spatially distinct compartment. This programmed collapse depends on the transcription factor Ndt80, conserved ER membrane structuring proteins Lnp1 and reticulons, and the actin cytoskeleton. A subset of ER is retained at the mother cell plasma membrane and excluded from gamete cells via the action of ER–plasma membrane tethering proteins. ER remodeling is coupled to ER degradation by selective autophagy, which relies on ER collapse and is regulated by timed expression of the autophagy receptor Atg40. Thus, developmentally programmed changes in ER morphology determine the selective degradation or inheritance of ER subdomains by gametes.

Meiotic resetting of the cellular Sod1 pool is driven by protein aggregation, degradation, and transient LUTI-mediated repression

“…It also involves clearance of cellular damage, resulting in gametes that act as "young" cells, regardless of progenitor cell age (Ünal et al, 2011). The factors that contribute to this natural rejuvenation are not yet known, but removal of preexisting nuclear, mitochondrial, and ER proteins has recently been shown to accompany the meiotic program (Sawyer et al, 2019;King and Goodman et al, 2019;Otto et al, 2021). It is intriguing that, more broadly, many abundant "housekeeping" proteins are degraded during the meiotic program in budding yeast and resynthesized prior to gamete maturation (Eisenberg and Higdon et al, 2018).…”

Life and Death Decisions—The Many Faces of Autophagy in Cell Survival and Cell Death

“…For example, during yeast meiosis, the level of Atg40, the reticulophagy (selective autophagy of the endoplasmic reticulum [ER]) receptor, is induced, and reticulophagy is activated to remove a subset of this organelle. The loss of Atg40 and most of the Atg proteins leads to decreased sporulation efficiency [ 27 ]. In mammals, mitophagy is responsible for the clearance of mitochondria during the maturation of erythroid cells, and blocking mitophagy leads to reduced mature erythrocytes, causing anemia as well as shorter lifespan in mice [ 28 , 29 ].…”

Spatiotemporal Dynamic Regulation of Organelles During Meiotic Development, Insights From Fungi

“…In addition to the NE, the peripheral ER domains also undergo dynamic meiotic remodeling. Akin to mitochondria, regulated changes in ER arrangement and distribution facilitate its selective meiotic inheritance ( Suda et al, 2007 ; Otto et al, 2021 ). During S. cerevisiae early meiosis, most cortical ER coalesces and is subsequently relocated to the cell central area by anaphase II–in a process called ER collapse–, to be ultimately segregated into ascospores.…”

“…During this process, certain ER domains remain attached to plasma membrane by the tricalbins and Ist2 tethering proteins. Consequently, these domains are excluded from ascospores upon their formation, and are later degraded by vacuolar lysis ( Otto et al, 2021 ). Like mitochondria, detachment of the ER from the plasma membrane depends on the transcriptional regulator Ndt80.…”

“…In addition, ER detachment requires the reticulon and Yop1 proteins–which shape the ER by promoting membrane curvature–, as well as the lunapark protein Lnp1, which regulates ER network formation. ER collapse depends on actin dynamics and is followed by the elimination of a second subset of ER by selective ER autophagy (ER-phagy), which defines the ER to be segregated into ascospores ( Otto et al, 2021 ). These findings revealed that meiotic inheritance of the ER relies on a sophisticated system that involves two parallel pathways for ER degradation, which selectively eliminate distinct ER subdomains, most probably as a quality control mechanism ensuring progeny rejuvenation.…”