Biology subjects

Bohnert, K. A.

Publications and source records attributed to Bohnert, K. A..

7 recordsLinked to original sources

bioRxiv2026

Release of BEC-1 from CED-9 stimulates lysosome tubulation in C. elegans by engaging Class III PI3K complex I

The anti-apoptotic protein CED-9 and the autophagy protein BEC-1 have been linked to autophagy regulation, but how their interaction modulates this process is not fully understood. Here, we find that the physical dissociation of BEC-1 from CED-9 influences lysosomal morphology in addition to autophagic activity in Caenorhabditis elegans. We present evidence that when autophagy is stimulated via dietary restriction, BEC-1 is released from CED-9 and assembles with VPS-34 and other members of the PI3K complex I to promote PI3P enrichment at lysosomal membranes and subsequent membrane tubulation. Mutation of two hydrophobic amino acids within a predicted BH-3 like motif of BEC-1 is sufficient to disrupt its interaction with CED-9, thereby constitutively inducing lysosomal tubulation and increasing autophagic cargo turnover. This phenotype is dependent on VPS-34 activity, linking the CED-9/BEC-1 dissociation to PI3K-dependent lysosomal remodeling. Collectively, our work identifies the CED-9/BEC-1 interaction as a molecular switch that governs apoptosis, autophagy, and lysosomal morphology.

cell biology↗

bioRxiv2025

Inhibition of peroxisomal protein PRX-11 promotes longevity in Caenorhabditis elegans via enhancements to mitochondria

Peroxisomes execute essential functions in cells, including detoxification and lipid oxidation. Despite their centrality to cell biology, the relevance of peroxisomes to aging remains understudied. We recently reported that peroxisomes are degraded en masse via pexophagy during early aging in the nematode Caenorhabditis elegans, and we found that downregulating the peroxisome-fission protein PRX-11/PEX11 prevents this age-dependent pexophagy and extends lifespan. Here, we further investigated how prx-11 inhibition promotes longevity. Remarkably, we found that reducing peroxisome degradation with age led to concurrent improvements in another organelle: mitochondria. Animals lacking prx-11 function showed tubular, youthful mitochondria in older ages, and these enhancements required multiple factors involved in mitochondrial tubulation and biogenesis, including FZO-1/Mitofusin, UNC-43 protein kinase, and DAF- 16/FOXO. Importantly, mutation of each of these factors negated lifespan extension in prx-11-defective animals, indicating that pexophagy inhibition promotes longevity only if mitochondrial health is co-maintained. Our data support a model in which peroxisomes and mitochondria track together with age and interdependently influence animal lifespan.

cell biology↗

bioRxiv2023

The fission yeast cytokinetic ring component Fic1 promotes septum formation

In Schizosaccharomyces pombe septum formation is coordinated with cytokinetic ring constriction but the mechanisms linking these events are unclear. In this study, we explored the role of the cytokinetic ring component Fic1, first identified by its interaction with the F-BAR protein Cdc15, in septum formation. We found that the fic1 phospho-ablating mutant, fic1-2A, is a gain-of-function allele that suppresses myo2-E1, the temperature-sensitive allele of the essential type-II myosin, myo2. This suppression is achieved by the promotion of septum formation and required Fic1s interaction with the F-BAR proteins Cdc15 and Imp2. Additionally, we found that Fic1 interacts with Cyk3 and that this interaction was likewise required for Fic1s role in septum formation. Fic1, Cdc15, Imp2, and Cyk3 are the orthologs of the Saccharomyces cerevisiae ingression progression complex, which stimulates the chitin synthase Chs2 to promote primary septum formation. However, our findings indicate that Fic1 promotes septum formation and cell abscission independently of the S. pombe Chs2 ortholog. Thus, while similar complexes exist in the two yeasts that each promote septation, they appear to have different downstream effectors. Summary StatementThe S. pombe cytokinetic ring protein Fic1 promotes septum formation in a manner dependent on interactions with the cytokinetic ring components Cdc15, Imp2, and Cyk3.

cell biology↗

bioRxiv2022

VCP acts downstream of tTAFs to downregulate mono-ubiquitinated H2A and promote spermatocyte differentiation in Drosophila

Valosin-containing protein (VCP) binds and extracts ubiquitinated cargo to regulate protein homeostasis. While VCP has been studied primarily in aging and disease contexts, it also affects germline development. However, the precise molecular functions of VCP in the germline, particularly in males, are poorly understood. Using the Drosophila male germline as a model system, we find that VCP translocates from the cytosol to the nucleus as germ cells transition into the meiotic spermatocyte stage. Importantly, nuclear translocation of VCP appears to be one critical event stimulated by testis-specific TBP-associated factors (tTAFs) to drive spermatocyte differentiation. Like tTAF mutants, spermatocyte gene expression fails to properly activate in VCP-RNAi testes, and germ cells arrest in early meiosis. At a molecular level, VCP activity supports spermatocyte gene expression by downregulating a repressive histone modification, mono-ubiquitinated H2A (H2Aub), at this developmental transition. Remarkably, experimentally blocking H2Aub in VCP-RNAi testes is sufficient to overcome the meiotic-arrest phenotype and to promote development through meiosis. Collectively, our data highlight VCP as a novel downstream effector of tTAFs that downregulates H2Aub to facilitate meiotic progression. SUMMARY STATEMENTVCP promotes the downregulation of mono-ubiquitinated H2A (H2Aub), potentially by driving H2A turnover. VCP-dependent downregulation of H2Aub occurs downstream of testis-specific TBP-associated factors and supports spermatocyte gene expression and differentiation.

developmental biology↗

bioRxiv2022

Reproductive tradeoffs govern sexually dimorphic tubular lysosome induction in C. elegans

Animals of different sexes often exhibit unique behaviors that benefit their specific reproductive interests. In the nematode Caenorhabditis elegans, self-fertilizing hermaphrodites can reproduce without a mate and thus prioritize feeding to satisfy the high energetic costs of reproduction. However, males, which rely on finding potential mates for reproduction, sacrifice feeding and instead prioritize exploratory behavior. Here, we demonstrate that these differences in behavior are linked to sexual dimorphism at the cellular level; young males raised on a rich food source show constitutive induction of gut tubular lysosomes, a non-canonical lysosome morphology that typically forms in the gut of young hermaphrodites only when food is limited. We find that male-specific induction of gut tubular lysosomes on abundant food is due to self-imposed dietary restriction through daf-7/TGF{beta} signaling, which promotes mate-searching at the cost of feeding. While gut tubular lysosomes are largely absent from well-fed hermaphrodites at the start of adulthood, their induction accelerates in hermaphrodites in early aging, dependent on the presence of sperm and, partly, on embryo production. These findings identify tubular lysosome induction as a sexually dimorphic cellular event that may integrate animal physiology with sex-specific behavioral differences important for reproductive success.

cell biology↗

bioRxiv2021

Tubular lysosome induction couples animal starvation to healthy aging

Dietary restriction promotes longevity via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Using the nematode Caenorhabditis elegans, we show that induction of autophagic tubular lysosomes, which occurs upon dietary restriction or mTOR inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces tubular lysosomes not only in affected individuals but also in well-fed descendants, and the presence of gut tubular lysosomes in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila SVIP, a tubular-lysosome activator in flies, artificially induces tubular lysosomes in well-fed worms and improves C. elegans health in old age. These findings identify tubular lysosomes as a new class of lysosomes that couples starvation to healthy aging. One-Sentence SummaryTubular lysosome induction promotes healthy aging.

cell biology↗

bioRxiv2020

A genetic screen identifies processes that couple oocyte maturation to proteostasis in the immortal C. elegans germ lineage

Somatic cells age and die, but the germ-cell lineage is immortal. In C. elegans, germline immortality involves proteostasis renewal at the beginning of each new generation, when oocyte-maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen. Oocyte maturation signals are known to trigger protein-aggregate removal via lysosome acidification. Our findings suggest that lysosomes are acidified as a consequence of changes in ER activity that permit assembly of the lysosomal V-ATPase, which in turn allows lysosomes to clear the aggregates via microautophagy. We define two functions for mitochondria, both of which appear to be independent of ATP generation. Many genes from the screen also regulate lysosome acidification and age-dependent protein aggregation in the soma, suggesting a fundamental mechanistic link between proteostasis renewal in the germline and somatic longevity.

cell biology↗