Shimin Zhao

Shimin Zhao

Professor,School of Life Sciences, Fudan University

Title：

Metabolites deregulation and human diseases

Abstract：Besides being energetic and biosynthetic cues, metabolites are signaling molecules that regulate cell signaling through non-covalent binding or covalent post translational modification to proteins that are functioning in diverse range of signaling pathways. Inhibition of a-ketoglutarate (a-KG) – dependent dioxygenases through decreasing cellular a-KG levels or accumulating a-KG structural analogous metabolites, such as 2-hydroxyglutarate, sucinate and fumarate, by metabolic enzymes mutations alters cancer-associated signaling pathways such as HIF1a pathway and epigenetic functions such as histones and DNA methylation. Moreover, metabolic enzymes mutations that accumulate a-KG analogous that induce hypersuccinylation, which preferentially impairs mitochondria respiration and induces the Warburg effect-like metabolism in cells. This, together with that hypersuccinylation induces apoptosis resistance by overexpressing BCL-2, accounts for the tumorigenicities of a-KG

analogous metabolites. Our results highlight role of altered metabolites sensing and provides possibilities of novel cancer treatment approaches through intervening metabolites-protein interactions.