When location makes oxidative stress lethal: mitoxyperilysis at the immunometabolic stress interface
- 1Rehabilitation Department, The People’s Hospital Medical Group of Xiangzhou
- 2Department of Intensive Care Unit, The People’s Hospital Medical Group of Xiangzhou
Abstract
Mitoxyperilysis is a proposed lytic death pathway in which oxidatively damaged mitochondria become membrane-lethal when retained at the plasma membrane. In founding models, TLR stimulation plus carbon restriction engaged MYD88-dependent innate signalling and BAX/BAK1/BID-dependent mitochondrial oxidative stress, while mTORC2–RhoA–actin remodelling prolonged peripheral mitochondrial retention. Mitoxyperiosis denotes prolonged mitochondria-plasma membrane association and localised oxidative membrane injury, whereas mitoxyperilysis denotes the subsequent plasma membrane rupture and lytic cell death. In these models, NINJ1 contributed to terminal rupture and LDH/HMGB1 release without being required for cell death. The damaging oxidant, physical tether, and mechanism linking local injury to membrane failure remain unresolved. Sepsis may reproduce upstream metabolic-redox conditions, but direct evidence for the complete spatial sequence in patient-derived cells is lacking. This review separates founding-model findings from disease-relevant observations and untested steps.
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BibTeX
@article{zhang2026when,
title = {{When location makes oxidative stress lethal: mitoxyperilysis at the immunometabolic stress interface}},
author = {Yu Zhang and Xin Ping Xia and Ling Zhao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1991494},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1991494/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - When location makes oxidative stress lethal: mitoxyperilysis at the immunometabolic stress interface
AU - Yu Zhang
AU - Xin Ping Xia
AU - Ling Zhao
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1991494
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1991494/full
AB - Mitoxyperilysis is a proposed lytic death pathway in which oxidatively damaged mitochondria become membrane-lethal when retained at the plasma membrane. In founding models, TLR stimulation plus carbon restriction engaged MYD88-dependent innate signalling and BAX/BAK1/BID-dependent mitochondrial oxidative stress, while mTORC2–RhoA–actin remodelling prolonged peripheral mitochondrial retention. Mitoxyperiosis denotes prolonged mitochondria-plasma membrane association and localised oxidative membrane injury, whereas mitoxyperilysis denotes the subsequent plasma membrane rupture and lytic cell death. In these models, NINJ1 contributed to terminal rupture and LDH/HMGB1 release without being required for cell death. The damaging oxidant, physical tether, and mechanism linking local injury to membrane failure remain unresolved. Sepsis may reproduce upstream metabolic-redox conditions, but direct evidence for the complete spatial sequence in patient-derived cells is lacking. This review separates founding-model findings from disease-relevant observations and untested steps.
SN - 1664-3224
ER -