Year: 2024
Type: conference-abstract
Abstract: Lysosomes (or vacuoles in yeast) are acidic organelles that function in protein degradation as well as metabolite storage and signaling. Impaired lysosomal function is a hallmark of aging across species and is a major contributor to age-related cellular dysfunction. Because many pathways converge at the lysosome that rely on the acidification of the organelle, how perturbation in lysosome acidity impacts cell function is incompletely understood. We recently used budding yeast as a model system to interrogate how vacuole dysfunction impacts cell health during aging, with a specific focus on dissecting the nature of its functional link to another metabolic organelle, the mitochondrion. We found that the essential function of vacuoles in supporting mitochondrial respiration is not linked to its well-known function in autophagy, but rather, it was tied to the role of vacuoles in amino acid compartmentalization and storage. We found that cysteine, which is stored in vacuoles in healthy cells, disrupts iron homeostasis when its vacuole compartmentation is perturbed during aging. Loss of iron homeostasis in turn alters the function of mitochondria, as well as numerous other iron-dependent cellular processes. Importantly, the connection between lysosome function, mitochondria, and iron homeostasis has also been observed by two other groups in human cells. Altogether, these results raise a new hypothesis to explain how loss of lysosome function impacts cell health, through alterations in amino acid and iron homeostasis. In this talk, I will discuss our recent work in this area focused on identifying pathways that collaborate with vacuoles to maintain intracellular iron and amino acid homeostasis.
Source: Journal of Biological Chemistry
Author: Adam Hughes
Institution: University of Utah
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
OpenAlex ID: W4393167888