Biology subjects

Caudron, F.

Publications and source records attributed to Caudron, F..

3 recordsLinked to original sources

bioRxiv2026

Dynamics of phosphofructokinase condensation are regulated by metabolic and redox cues

Condensation of phosphofructokinase, the rate-limiting enzyme of glycolysis, into granules has been observed across species and in various stress conditions. However, it remains unclear what mechanisms govern this process. Here, we show that the two subunits of yeast phosphofructokinase, Pfk1 and Pfk2, assemble into granules even in the absence of exogenous stress, challenging the notion that PFK condensation in yeast is restricted to quiescent or stressed cells. While phosphofructokinase granules are predominant in replicatively aged cells, they are independent of cell division and can form before or after cells cease dividing. We further demonstrate that both subunits can co-localise to the same granules and that Pfk2 requires the disordered N-terminus of Pfk1 for assembly. Strikingly, phosphofructokinase granules are largely absent in cells engaged in respiration or lacking respiratory capacity, but their formation is strongly induced during the metabolic transition from fermentation to respiration. This suggests that phosphofructokinase condensation is tightly linked to the metabolic strategy of the cell. Moreover, we find that reactive oxygen species signaling, mediated by superoxide dismutase 1 (Sod1), modulates phosphofructokinase granule formation, as cells deficient in Sod1 exhibit impaired granule assembly. Overall, our results indicate that phosphofructokinase condensation is a dynamic process regulated by metabolic and redox cues.

cell biology↗

bioRxiv2021

A rare natural lipid induces neuroglobin expression to prevent amyloid oligomers toxicity and retinal neurodegeneration.

Most neurodegenerative diseases such as Alzheimers disease are proteinopathies linked to the toxicity of amyloid oligomers. Treatments to delay or cure these diseases are lacking. Using budding yeast, we report that the natural lipid tripentadecanoin induces expression of the nitric oxide oxidoreductase Yhb1 to prevent the formation of protein aggregates during aging and extends replicative lifespan. In mammals, tripentadecanoin induces expression of the Yhb1 orthologue, neuroglobin, to protect neurons against amyloid toxicity. Tripentadecanoin also rescues photoreceptors in a mouse model of retinal degeneration and retinal ganglion cells in a Rhesus monkey model of optic atrophy. Together, we propose that tripentadecanoin affects p-bodies to induce neuroglobin expression and offers a potential treatment for proteinopathies and retinal neurodegeneration. One Sentence SummaryThe natural lipid tripentadecanoin is cytoprotective against amyloid oligomer toxicity and retinal neurodegeneration by inducing YHBI/neuroglobin expression in yeast and mammals.

cell biology↗

bioRxiv2020

A mechanism to prevent transformation of the Whi3 mnemon into a prion.

In response to deceptive courtship, budding yeast cells escape pheromone induced cell cycle arrest through coalescence of the G1/S inhibitor Whi3 into a dominant inactive super-assembly. Strikingly, Whi3 super-assemblies remain stable over many cell cycles in the mother cells and are not passed on to the daughter cells. Thereby, Whi3 coalescence encodes memory, conferring to it the property of a mnemon (Whi3mnem), a protein which conformational change maintain a trait that is permanent in the mother cell but is not inherited by daughter cells. Mnemons share structural features with prions, which are self-templating protein conformations that are inherited by daughter cells. Yet, how the maintenance and asymmetric inheritance of Whi3mnem are achieved is unknown. Here, we report that Whi3mnem is closely associated with endoplasmic reticulum (ER) membranes and retained in the mother cell by the presence of lateral membrane diffusion barriers at the bud neck. Strikingly, barrier defects made Whi3mnem propagate in a mitotically stable manner, like a prion. Alike Whi3mnem, transformation of Whi3 into a prion required its poly-glutamine prion-like domain. Thus, we propose that Whi3mnem is in a self-templating state, lending temporal stability to the memory that it encodes, while its anchorage into the compartmentalized membranes of the ER ensures its confinement in the mother cell and prevents its infectious propagation. These results suggest that confined self-templating super-assembly is a powerful mechanism for the long-term encoding of information.

cell biology↗