Biology subjects

McColl, G.

Publications and source records attributed to McColl, G..

3 recordsLinked to original sources

bioRxiv2024

Dietary zinc limitation dictates lifespan and reproduction trade-offs of Drosophila mothers

Dietary metal ions significantly influence the lifespan and reproduction of Drosophila females. In this study, we show that while the depletion of all metal ions from the diet adversely affects reproduction and lifespan, the absence of Zn alone negatively impacts reproduction without adversely altering maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Although our data show that flies sense varying dietary Zn levels, they apparently do not alter their feeding preferences to optimise egg production when faced with a choice between Zn- depleted or Zn- sufficient food, but they can choose to preferentially oviposit on Zn containing food, perhaps indicating a strategy to assure offspring survival. We also uncovered a role for the white gene in sustaining high levels of egg viability when Zn is diluted in the diet. These insights into the role of dietary metal ions, particularly Zn, point to a central role for these dietary micronutrients to indicate environmental quality and so govern trade-offs between lifespan and reproduction in flies.

evolutionary biology↗

bioRxiv2021

A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells

An extensive network of chaperones and other proteins maintain protein homeostasis and guard against inappropriate protein aggregation that is a hallmark of neurodegenerative diseases. Using a fluorescence resonance energy-based biosensor that simultaneously reports on intact cellular chaperone holdase activity and detrimental aggregation propensity, we investigated the buffering capacity of the systems managing protein homeostasis in the nucleus of the human cell line HEK293 compared to the cytosol. We found that the nucleus showed lower net holdase activity and reduced capacity to suppress protein aggregation, suggesting that the nuclear quality control resources are less effective compared to those in the cytosol. Aggregation of mutant huntingtin exon 1 protein (Httex1) in the cytosol appeared to deplete cytosolic chaperone supply by depleting holdase activity. Unexpectedly, the same stress increased holdase activity in the nucleus suggesting that proteostasis stress can trigger a rebalance of chaperone supply in different subcellular compartments. Collectively the findings suggest the cytosol has more capacity to manage imbalances in proteome foldedness than the nucleus, but chaperone supply can be redirected into the nucleus under conditions of proteostasis stress caused by cytosolic protein aggregation.

biochemistry↗

bioRxiv2019

Ferrous-glutathione coupling mediates ferroptosis and frailty in Caenorhabditis elegans

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis1, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in the Caenorhabditis elegans model of ageing2. Here we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan in C. elegans. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant ageing rate. Because excess age-related iron elevation in somatic tissue, particularly in brain3-5, is thought to contribute to degenerative disease6, 7, our data indicate that post-developmental interventions to limit ferroptosis may promote healthy ageing.

molecular biology↗