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Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts
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Iron loss triggers mitophagy through induction of mitochondrial ferritin

Yuichi Hara1, Izumi Yanatori2,3, Atsushi Tanaka4

  • 1Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan.

EMBO Reports
|September 25, 2020
PubMed

Insights

Iron loss triggers mitophagy, the removal of damaged mitochondria, via mitochondrial ferritin (FTMT). This process, enhanced by deferiprone, suppressed liver cancer in mice, offering therapeutic potential.

Area of Science:

  • Cellular Biology
  • Mitochondrial Dynamics
  • Autophagy

Background:

  • Mitochondrial quality control is crucial and relies on mitophagy.
  • Impaired mitophagy is linked to aging and diseases.
  • Iron loss can induce mitophagy through unknown mechanisms.

Purpose of the Study:

  • To elucidate the mechanism by which iron loss triggers mitophagy.
  • To investigate the therapeutic potential of iron chelator-induced mitophagy.

Main Methods:

  • Utilized deferiprone (iron chelator) treatment in cellular and mouse models.
  • Investigated the role of mitochondrial ferritin (FTMT), Specific protein 1, and hypoxia-inducible factor 1α.
  • Examined the interaction between FTMT and nuclear receptor coactivator 4.
  • Assessed mitophagy in depolarized mitochondria and hepatocellular carcinoma (HCC) development.

Main Results:

  • Deferiprone treatment increased FTMT expression and its mitochondrial outer membrane localization.
  • Specific protein 1 and HIF-1α were essential for deferiprone-induced FTMT increase.
  • FTMT interacted with nuclear receptor coactivator 4, facilitating mitophagy of depolarized mitochondria.
  • Deferiprone suppressed HCC development in mice by inducing mitophagy, an effect abrogated by FTMT silencing.

Conclusions:

  • Iron loss induces mitophagy through a pathway involving FTMT, Specific protein 1, HIF-1α, and nuclear receptor coactivator 4.
  • Targeting mitophagy via iron loss presents a potential therapeutic strategy for conditions like HCC.
Keywords:
hepatocellular carcinomairon chelatormitochondriamitochondrial ferritinmitophagy

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