Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during yeast replicative aging
Abstract
Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition and signalling. While cellular aging is associated with functional changes across many cellular components contributing to the collective decline in cellular function, little is known about how it affects CME. Here we show that CME dynamics are significantly altered during replicative aging in budding yeast, with older cells having slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced cargo internalization. This change in CME dynamics is mother cell-specific and is not observed in daughter cells. We identified vacuolar pH, a key driver of aging phenotypes in budding yeast, as a central player in this modulation of CME dynamics during aging. Perturbing vacuolar pH in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. Finally, we demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. These findings establish vacuolar pH as a critical regulator of CME during cellular aging, and strengthen its role in the overall cellular aging process in budding yeast.
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Research summary
The paper investigates the role of vacuolar pH in regulating clathrin-mediated endocytosis (CME) during replicative aging in yeast, which is relevant to understanding cellular aging mechanisms. By identifying a specific cellular process affected by aging and linking it to a key aging-related factor (vacuolar pH), the study contributes to the broader understanding of aging at a cellular level. However, while the findings are solid and provide insights into the aging process, they are more incremental than groundbreaking, limiting their overall impact on the field of longevity research.
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