PI5P4Ks drive metabolic homeostasis through peroxisome-mitochondria interplay.

ABSTRACT: PI5P4Ks are a class of phosphoinositide kinases that phosphorylate PI-5-P to PI-4,5-P₂. Distinct localization of phosphoinositides is fundamental for a multitude of cellular functions. Here, we identify a role for peroxisomal PI-4,5-P₂ generated by the PI5P4Ks in maintaining energy balance. We demonstrate that PI-4,5-P₂ regulates peroxisomal fatty acid oxidation by mediating trafficking of lipid droplets to peroxisomes, which is essential for sustaining mitochondrial metabolism. Using fluorescent-tagged lipids and metabolite tracing, we show that loss of the PI5P4Ks significantly impairs lipid uptake and β-oxidation in the mitochondria. Further, loss of PI5P4Ks results in dramatic alterations in mitochondrial structural and functional integrity, which under

SUBMITTER: Ravi A 

PROVIDER: S-EPMC9012263 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature