Hexokinase regulates Mondo-mediated longevity via the PPP and organellar dynamics.

ABSTRACT: The transcriptional complex Mondo/Max-like, MML-1/MXL-2, acts as a convergent transcriptional regulatory output of multiple longevity pathways in Caenorhabditis elegans. These transcription factors coordinate nutrient sensing with carbohydrate and lipid metabolism across the evolutionary spectrum. While most studies have focused on the downstream outputs, little is known about the upstream inputs that regulate these transcription factors in a live organism. Here, we found that knockdown of various glucose metabolic enzymes decreases MML-1 localization in the nucleus and identified two hexokinase isozymes, hxk-1 and hxk-2, as the most vigorous regulators of MML-1 function. Upon hexokinase knockdown, MML-1 redistributes to mitochondria and lipid droplets (LDs), and conco

SUBMITTER: Laboy R 

PROVIDER: S-EPMC12339002 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature