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Updated: Dec 30, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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AIFM2 blocks ferroptosis independent of ubiquinol metabolism

Enyong Dai1, Wenlong Zhang1, Dan Cong1

  • 1Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130031, China.

Biochemical and Biophysical Research Communications
|January 23, 2020
PubMed

Insights

Apoptosis-inducing factor mitochondria-associated 2 (AIFM2) suppresses ferroptosis by recruiting ESCRT-III to repair cell membranes, independent of ubiquinol. Inhibiting this pathway enhances cancer therapy effectiveness.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • Ferroptosis is a regulated cell death pathway implicated in cancer.
  • Cancer cells develop ferroptosis resistance via protein expression changes.
  • The mechanism of ferroptosis suppressor AIFM2 (Apoptosis-inducing factor mitochondria-associated 2) was unclear.

Purpose of the Study:

  • To elucidate the mechanism by which AIFM2 suppresses ferroptosis.
  • To investigate the role of AIFM2 in ferroptosis resistance.
  • To assess the therapeutic potential of targeting the AIFM2 pathway in cancer.

Main Methods:

  • Investigated AIFM2's role in ferroptosis using cell culture models.
  • Analyzed AIFM2's interaction with ubiquinol and ESCRT-III.
  • Utilized a xenograft tumor mouse model to evaluate therapeutic inhibition.

Main Results:

  • AIFM2 inhibits ferroptosis independently of ubiquinol.
  • AIFM2-dependent ESCRT-III recruitment to the plasma membrane mediates ferroptosis resistance via membrane repair.
  • Genetic inhibition of the AIFM2-ESCRT-III pathway potentiated sorafenib's anticancer activity in vivo.

Conclusions:

  • AIFM2 confers ferroptosis resistance through an ESCRT-III-mediated membrane repair pathway.
  • Targeting the AIFM2-ESCRT-III axis represents a potential strategy to overcome ferroptosis resistance in cancer therapy.
Keywords:
AIFM2CoQ10ESCRTFerroptosisLipid peroxidationUbiquinol

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