SUSTech.edu.cn EN

Speaker: Prof.Quan CHEN(Nankai University)

Time: 12:30-13:30,Dec. 20,2019

Venue: The second floor of Starbucks Coffee,opposite to the Library

Molecular regulation of selective mitophagy and its role in inflammasome activation and hepatocarcinogenesis

Abstract:

Accumulating evidence has proved that mitochondrial metabolism and functions are closely linked with tumor initiation and progression. Mitophagy, a selective process that removes damaged or unwanted mitochondria, was suggested to play a role in mitochondrial quality control and metabolic reprogramming. We have revealed that FUNDC1, a mitochondrial outer-membrane protein, functions as a mitophagy receptor to mediate hypoxia-induced mitophagy. FUNDC1 harbors an LC-3 –interacting region (LIR) and interacts with LC-3 to mediate mitophagy both in cultured cell systems and in (patho-)physiological settings. We further showed that enhanced expression of FUNDC1 protects against diethylnitrosamine (DEN)-induced HCC, whereas specific knockout of FUNDC1 in hepatocytes promotes HCC initiation and progression. Hepatocyte-specific FUNDC1 ablation results in the accumulation of damaged mitochondria and elicits a cascade of events involving inflammosome activation, leading to hyperproliferation of hepatocytes and promotion of hepatocellular carcinoma. Our results uncover the critical role of FUNDC1-mediated mitophagy in inflammasome activation and hepatocarcinogenesis.


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