Li 2020 Cells

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Li M, Wang L, Wang Y, Zhang S, Zhou G, Lieshout R, Ma B, Liu J, Qu C, Verstegen MMA, Sprengers D, Kwekkeboom J, van der Laan LJW, Cao W, Peppelenbosch MP, Pan Q (2020) Mitochondrial fusion via OPA1 and MFN1 supports liver tumor cell metabolism and growth. Cells 9:E121.

» PMID: 31947947 Open Access

Li Meng, Wang Ling, Wang Yijin, Zhang Shaoshi, Zhou Guoying, Lieshout Ruby, Ma Buyun, Liu Jiaye, Qu Changbo, Verstegen Monique MA, Sprengers Dave, Kwekkeboom Jaap, van der Laan Luc JW, Cao Wanlu, Peppelenbosch Maikel P, Pan Qiuwei (2020) Cells

Abstract: Metabolic reprogramming universally occurs in cancer. Mitochondria act as the hubs of bioenergetics and metabolism. The morphodynamics of mitochondria, comprised of fusion and fission processes, are closely associated with mitochondrial functions and are often dysregulated in cancer. In this study, we aim to investigate the mitochondrial morphodynamics and its functional consequences in human liver cancer. We observed excessive activation of mitochondrial fusion in tumor tissues from hepatocellular carcinoma (HCC) patients and in vitro cultured tumor organoids from cholangiocarcinoma (CCA). The knockdown of the fusion regulator genes, OPA1 (Optic atrophy 1) or MFN1 (Mitofusin 1), inhibited the fusion process in HCC cell lines and CCA tumor organoids. This resulted in inhibition of cell growth in vitro and tumor formation in vivo, after tumor cell engraftment in mice. This inhibitory effect is associated with the induction of cell apoptosis, but not related to cell cycle arrest. Genome-wide transcriptomic profiling revealed that the inhibition of fusion predominately affected cellular metabolic pathways. This was further confirmed by the blocking of mitochondrial fusion which attenuated oxygen consumption and cellular ATP production of tumor cells. In conclusion, increased mitochondrial fusion in liver cancer alters metabolism and fuels tumor cell growth.

Keywords: MFN1, OPA1, Liver cancer, Mitochondrial dynamics Bioblast editor: Plangger M


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression  Pathology: Cancer 

Organism: Human  Tissue;cell: Liver  Preparation: Intact cells 



HRR: Oxygraph-2k 

Labels, 2020, CN