Vitamin B₆ is governed by the local compartmentalization of metabolic enzymes during growth.

ABSTRACT: Vitamin B₆ is a vital micronutrient across cell types and tissues, and dysregulated B₆ levels contribute to human disease. Despite its importance, how B₆ vitamer levels are regulated is not well understood. Here, we provide evidence that B₆ dynamics are rapidly tuned by precise compartmentation of pyridoxal kinase (PDXK), the rate-limiting B₆ enzyme. We show that canonical Wnt rapidly led to the accumulation of inactive B₆ by shunting cytosolic PDXK into lysosomes. PDXK was modified with methyl-arginine Degron (MrDegron), a protein tag for lysosomes, which enabled delivery via microautophagy. Hyperactive lysosomes resulted in the continuous degradation of PDXK and B₆ deficiency that promoted proliferation in Wnt-d

SUBMITTER: Franco CN 

PROVIDER: S-EPMC10491294 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature