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Updated: Feb 18, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
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CypD Dependent mPTP Opening Is Crucial for Oxidized Mitochondrial DNA Release in Ferroptosis

Hong Zhou1, Wan Fu1, Shizuo Liu1

  • 1Institute For Translational Medicine On Cell Fate and Disease, Department of Pathophysiology, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 17, 2026
PubMed

Insights

Mitochondrial permeability transition pore (mPTP) opening drives ferroptosis by releasing oxidized mitochondrial DNA (mtDNA). This mtDNA activates the cGAS-STING pathway, promoting cell death and tumor suppression.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ferroptosis is regulated cell death marked by lipid peroxide accumulation and mitochondrial dysfunction.
  • The precise mechanisms causing mitochondrial swelling and its role in ferroptosis signaling are not fully understood.

Purpose of the Study:

  • To elucidate the role of mitochondrial permeability transition pore (mPTP) opening in ferroptosis.
  • To investigate the function of released mitochondrial DNA (mtDNA) in ferroptosis signaling.

Main Methods:

  • Investigated mPTP opening during ferroptosis.
  • Analyzed the release and signaling of oxidized mitochondrial DNA (mtDNA).
  • Utilized mouse xenograft tumor models to assess therapeutic potential.

Main Results:

  • mPTP opening is essential for mitochondrial swelling and ferroptosis activation.
  • Oxidized mtDNA released via mPTP activates the cGAS-STING pathway.
  • Inhibition of mtDNA repair enhances ferroptosis sensitivity and tumor suppression.

Conclusions:

  • mPTP acts as a critical mediator in ferroptosis by releasing mtDNA.
  • Released mtDNA functions as a signaling molecule activating the cGAS-STING pathway to promote ferroptosis.
  • Targeting mtDNA repair may enhance ferroptosis-based cancer therapies.
Keywords:
cGAS‐STINGferroptosismPTPmitochondriamtDNA

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