Loss of vacuolar acidity results in iron-sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae.

ABSTRACT: The loss of vacuolar/lysosomal acidity is an early event during aging that has been linked to mitochondrial dysfunction. However, it is unclear how loss of vacuolar acidity results in age-related dysfunction. Through unbiased genetic screens, we determined that increased iron uptake can suppress the mitochondrial respiratory deficiency phenotype of yeast vma mutants, which have lost vacuolar acidity due to genetic disruption of the vacuolar ATPase proton pump. Yeast vma mutants exhibited nuclear localization of Aft1, which turns on the iron regulon in response to iron-sulfur cluster (ISC) deficiency. This led us to find that loss of vacuolar acidity with age in wild-type yeast causes ISC defects and a DNA damage response. Using microfluidics to investigate aging at the single-cell level, w

SUBMITTER: Chen KL 

PROVIDER: S-EPMC7205917 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature