【Publication Archive】 Study focusing on iron metabolism and mitophagy for the treatment of NASH and HCC published in EMBO Rep.

Please take a look at published study focusing on intracellular iron metabolism and mitophagy as therapeutic targets for hepatocellular carcinoma and non-alcoholic steatohepatitis (NASH).


Title: Iron loss triggers mitophagy through induction of mitochondrial ferritin

► Full text LINK [Hara Y et al., EMBO Rep. 2020]


In this paper, it has been shown that induction of mitophagy in hepatocytes by iron chelators suppresses the development of HCC, and iron chelator intake has been shown to promote mitophagy and suppress the development of HCC in STAM™ mice.


[ Summary ]

The results of iron chelation induced iron deficiency in hepatocytes are as follows:

  • Mitochondrial ferritin (MTFT) increased via the hypoxia-inducible factor-1α (HIF1α)-specific protein 1 (SP1) pathway.
  • FTMT interacted specifically with nuclear receptor coactivator 4 (NCOA4), a cargo receptor for autophagy
  • Mitophagy occurred selectively for depolarized mitochondria
  • HCC development was suppressed.


Since this study intervened in STAM mice in the phase in which they begin to form NASH pathology, it is suggested that the intake of iron chelators and promotion of mitophagy can prevent NASH as well as HCC.


In general, autophagic degradation of ferritin, known as ferritinophagy, is an important function in maintaining intracellular iron levels. Thus, the FTMT-specific mitophagy observed in this study may also be part of ferritinophagy. In addition, it is reported that ferritinophagy positively regulates ferroptosis [Santana-Codina N. and Mancias JD., Pharmaceuticals (Basel). 2018]. Therefore, the contents of this study may provide insight into the research and development of prevention and treatment of NASH and HCC by ferroptosis.


If you have a project that focuses on ferotosis, ferritinophagy, mitophagy, or iron metabolism, why not try it out in vivo study using STAM™ mice?


If you are interested in learning more about STAM™ mice or our experience in pharmacological evaluation studies, please feel free to contact us.