Function of mitochondrial chaperone TRAP1 during progression of metabolic diseases

Abstract

TRAP1 is an ATP-dependent molecular chaperone found in the mitochondria and overexpressed in various human cancers. TRAP1 maintains mitochondrial integrity to increase cell death threshold upon various cellular stresses and reprograms mitochondrial metabolism to meet metabolic demand during tumorigenesis. Thus, targeting TRAP1 could be an efficient strategy for development of potent anticancer drugs with novel mode of drug action. We have developed various TRAP1 inhibitors targeting not only the ATP binding pocket but also allosteric drug binding site in TRAP1 as cancer therapeutics. Those inhibitors have also been utilized to understand TRAP1 functions during various metabolic diseases. In this talk, I will briefly introduce TRAP1 functions in cancer mitochondria and our inhibitors with or without the mitochondria-targeting drug delivery systems, and discuss about implication of TRAP1 in metabolic diseases.