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Peer-reviewedCC BY 4.0Frontiers in Immunology

Unraveling the pyroptosis-mitophagy axis: from molecular mechanisms to therapeutic opportunities

  • Jiaqi Ban1
  • Ranxing Chen1
  • Lihong Ao1
  • Hua Zhao1
  • Jun Li1
  • Yungeng Wei2
  • Guichuan Huang3
  1. 1School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University
  2. 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University
  3. 3Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University
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Abstract

Mitophagy and pyroptosis are central regulators of cell fate and inflammation, and they form a complex bidirectional network across many diseases. Mitophagy suppresses NLRP3 inflammasome activation by removing damaged mitochondria and thereby reducing mtROS and mtDNA release, which blocks pyroptosis. Conversely, pyroptosis can inhibit mitophagy by releasing inflammatory mediators and activating caspase-1, creating reinforcing or counterbalancing feedback loops. Signaling modules such as PINK1/Parkin, NOD2-RIPK2, Nrf2/HO-1, and AMPK critically modulate both mitophagy and pyroptosis. These processes interact broadly in organ injuries of the brain, liver, kidney, lung, bone, and heart to determine inflammation intensity and cell survival. Natural small molecules and traditional Chinese medicine that target the mitophagy–pyroptosis axis can modify pathological states including neurodegeneration, metabolic inflammation, and immune evasion, and thus represent a promising strategy for precision therapy.

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Cite

BibTeXRIS
BibTeX
@article{ban2026unraveling,
  title = {{Unraveling the pyroptosis-mitophagy axis: from molecular mechanisms to therapeutic opportunities}},
  author = {Jiaqi Ban and Ranxing Chen and Lihong Ao and Hua Zhao and Jun Li and Yungeng Wei and Guichuan Huang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1950578},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1950578/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Unraveling the pyroptosis-mitophagy axis: from molecular mechanisms to therapeutic opportunities
AU  - Jiaqi Ban
AU  - Ranxing Chen
AU  - Lihong Ao
AU  - Hua Zhao
AU  - Jun Li
AU  - Yungeng Wei
AU  - Guichuan Huang
PY  - 2026
DA  - 2026/10/13
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1950578
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1950578/full
AB  - Mitophagy and pyroptosis are central regulators of cell fate and inflammation, and they form a complex bidirectional network across many diseases. Mitophagy suppresses NLRP3 inflammasome activation by removing damaged mitochondria and thereby reducing mtROS and mtDNA release, which blocks pyroptosis. Conversely, pyroptosis can inhibit mitophagy by releasing inflammatory mediators and activating caspase-1, creating reinforcing or counterbalancing feedback loops. Signaling modules such as PINK1/Parkin, NOD2-RIPK2, Nrf2/HO-1, and AMPK critically modulate both mitophagy and pyroptosis. These processes interact broadly in organ injuries of the brain, liver, kidney, lung, bone, and heart to determine inflammation intensity and cell survival. Natural small molecules and traditional Chinese medicine that target the mitophagy–pyroptosis axis can modify pathological states including neurodegeneration, metabolic inflammation, and immune evasion, and thus represent a promising strategy for precision therapy.
SN  - 1664-3224
ER  -