Structure of mitochondrial pyruvate carrier and its inhibition mechanism.

ABSTRACT: The mitochondrial pyruvate carrier (MPC) governs the entry of pyruvate-a central metabolite that bridges cytosolic glycolysis with mitochondrial oxidative phosphorylation-into the mitochondrial matrix^1-5. It thus serves as a pivotal metabolic gatekeeper and has fundamental roles in cellular metabolism. Moreover, MPC is a key target for drugs aimed at managing diabetes, non-alcoholic steatohepatitis and neurodegenerative diseases^4-6. However, despite MPC's critical roles in both physiology and medicine, the molecular mechanisms underlying its transport function and how it is inhibited by drugs have remained largely unclear. Here our structural findings on human MPC define the architecture of this vital transporter, delineate its substrate-binding site and translocation

SUBMITTER: He Z 

PROVIDER: S-EPMC12043432 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature