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


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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