Biology subjects

Meinema, A. C.

Publications and source records attributed to Meinema, A. C..

3 recordsLinked to original sources

bioRxiv2024

Dissociation of the nuclear basket triggers chromosome loss in aging yeast

In many organisms, aging is a clear risk factor for chromosome mis-segregation, the main source of aneuploidy. Here, we report that old yeast cells lose chromosomes by partitioning them asymmetrically to their daughter cells together with the pre-existing (old) spindle pole body (SPB, centrosome equivalent in yeast). Strikingly, remodelling of the nuclear pore complex (NPC) and the displacement of its nuclear basket triggered these asymmetric chromosome segregation events. Simultaneously, nuclear basket displacement caused unspliced pre-mRNAs to leak into the cytoplasm. We show that removing the introns of three genes involved in chromosome segregation was sufficient to fully suppress chromosome loss in old cells. Promoting pre-mRNA leakage in young cells also caused asymmetric chromosome partitioning and loss through the same three introns. Therefore, we propose that basket displacement from NPCs and its consequences for pre-mRNA quality control are key triggers of aging phenotypes such as aneuploidy.

cell biology↗

bioRxiv2021

Specialization of chromatin-bound nuclear pore complexes promotes yeast aging

The nuclear pore complex (NPC) mediates nearly all exchanges between nucleus and cytoplasm, and changes composition in many species as the organism ages. However, how these changes arise and whether they contribute themselves to aging is poorly understood. We show that in replicatively aging yeast cells attachment of DNA circles to NPCs drives the displacement of the NPCs nuclear basket and cytoplasmic complexes. Remodeling of the NPC resulted from the regulation of basket components by SAGA, rather than from damages. These changes affected NPC interaction with mRNA export factors, without affecting the residence of import factors or engaging the NPC quality control machinery. Mutations preventing NPC remodeling extended the replicative lifespan of the cells. Thus, our data indicate that DNA circles accumulating in the mother cell drive aging at least in part by triggering NPC specialization. We suggest that antagonistic pleiotropic effects of NPC specialization are key drivers of aging.

cell biology↗

bioRxiv2018

Saccharomyces cerevisiae goes through distinct metabolic phases during its replicative lifespan

A comprehensive description of the phenotypic changes during cellular aging is key towards unraveling its causal forces. Using recently developed experimental tools, which previously had enabled us to map age related changes in proteome and transcriptome (Janssens et al., 2015), and model-based inference methods, here, we generated a comprehensive account of the metabolic changes during the entire replicative life of Saecharomyces cerevisiae. With age, we found decreasing metabolite levels, decreasing growth and substrate uptake rates accompanied by a switch from aerobic fermentation to a respiratory metabolism, with increased glycerol and acetate production. The identification of intracellular metabolic fluxes revealed an increase in redox cofactor turnover, likely to combat the increased production of reactive oxygen species. The identified metabolic changes possibly reflect a dynamic adaptation to the age-associated, non- homeostatic increase in volume. With metabolism being an important factor of the cellular phenotype, this work complements our recent mapping of the transcriptomic and proteomic changes towards a holistic description of the cellular processes during aging.

cell biology↗