Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency.

ABSTRACT: Citrin is a liver-specific mitochondrial aspartate-glutamate carrier encoded by SLC25A13. Citrin deficiency caused by SLC25A13 mutation results in carbohydrate toxicity, citrullinemia type II, and fatty liver diseases, the mechanisms of some of which remain unknown. Citrin shows a functional homolog in yeast aspartate-glutamate carrier (Agc1p) and agc1Δ yeasts are used as a model organism of citrin deficiency. Here, we found that agc1Δ yeasts decreased fat utilization, impaired NADH balance in peroxisomes, and decreased chronological lifespan. The activation of GPD1-mediated NAD+ regeneration in peroxisomes by GPD1 over-expression or activation of the malate-oxaloacetate NADH peroxisomal shuttle, by increasing flux in this NADH shuttle and over-expression of MDH3, resulted in lifespan exte

SUBMITTER: Chalermwat C 

PROVIDER: S-EPMC7151034 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature