Mitochondrial quality-control uncoupling in sepsis: a missing link to persistent immune hyporesponsiveness
- 1Department of Rehabilitation Medicine, The People’s Hospital Medical Group of Xiangzhou
- 2Department of Intensive Care Medicine, The People’s Hospital Medical Group of Xiangzhou
Abstract
Sepsis imposes competing demands for antimicrobial activity and organelle maintenance. Mitochondrial recovery requires coordinated damage containment, selective removal, lysosomal degradation and recycling, and functional replacement. We define mitochondrial quality-control uncoupling as a mismatch among these processes. When damage outpaces completed clearance, dysfunctional mitochondria retain redox and danger-signaling activity. When removal outpaces replacement, mitochondrial mass and spare respiratory capacity decline. Incomplete lysosomal processing can combine both phenotypes by removing mitochondria from the functional network while retaining undegraded cargo. Immune cells may therefore remain viable yet fail to increase metabolic and biosynthetic output during renewed challenge. Inhibitory immune signaling can further restrict substrate use and mitochondrial rebuilding, reinforcing mitochondrial and immune dysfunction. This framework reconciles divergent observations on mitophagy and explains how inflammation can coexist with ineffective host defense. We define state-matched longitudinal phenotyping as repeated, cell-type-specific assessment of damage burden, clearance completion, respiratory reserve and immune function over time. Such phenotyping could guide interventions toward the dominant defect rather than indiscriminately activating a single pathway.
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BibTeX
@article{zhang2026mitochondrial,
title = {{Mitochondrial quality-control uncoupling in sepsis: a missing link to persistent immune hyporesponsiveness}},
author = {Yu Zhang and Xin Ping Xia and Ling Zhao},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1982407},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982407/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mitochondrial quality-control uncoupling in sepsis: a missing link to persistent immune hyporesponsiveness
AU - Yu Zhang
AU - Xin Ping Xia
AU - Ling Zhao
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1982407
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982407/full
AB - Sepsis imposes competing demands for antimicrobial activity and organelle maintenance. Mitochondrial recovery requires coordinated damage containment, selective removal, lysosomal degradation and recycling, and functional replacement. We define mitochondrial quality-control uncoupling as a mismatch among these processes. When damage outpaces completed clearance, dysfunctional mitochondria retain redox and danger-signaling activity. When removal outpaces replacement, mitochondrial mass and spare respiratory capacity decline. Incomplete lysosomal processing can combine both phenotypes by removing mitochondria from the functional network while retaining undegraded cargo. Immune cells may therefore remain viable yet fail to increase metabolic and biosynthetic output during renewed challenge. Inhibitory immune signaling can further restrict substrate use and mitochondrial rebuilding, reinforcing mitochondrial and immune dysfunction. This framework reconciles divergent observations on mitophagy and explains how inflammation can coexist with ineffective host defense. We define state-matched longitudinal phenotyping as repeated, cell-type-specific assessment of damage burden, clearance completion, respiratory reserve and immune function over time. Such phenotyping could guide interventions toward the dominant defect rather than indiscriminately activating a single pathway.
SN - 1664-3224
ER -