Dynamic changes of mitochondrial homeostasis and immune-inflammatory signaling during hemorrhagic shock resuscitation associated ischemia–reperfusion injury
- 1Department of Anesthesiology, General Hospital of Central Theater Command of People's Liberation Army (PLA) Graduate Joint Training Base, School of Medicine, Wuhan University of Science and Technology
- 2General Hospital Base of Central Theater Command of People’s Liberation Army, Hubei University of Medicine
- 3Department of Anesthesiology, General Hospital of Central Theater Command of People's Liberation Army (PLA)
Abstract
Traumatic hemorrhagic shock is a common and life-threatening condition following severe trauma, characterized by reduced effective circulating blood volume and insufficient tissue perfusion, ultimately leading to an imbalance between oxygen supply and demand as well as progressive multi-organ dysfunction. Fluid resuscitation is essential for restoring hemodynamic stability; however, it may simultaneously trigger or aggravate ischemia-reperfusion injury (IRI). Emerging evidence suggests that disruption of mitochondrial homeostasis represents not only a critical cellular basis underlying organ injury during hemorrhagic shock resuscitation, but also an important driver of immune activation and inflammatory amplification. At the level of mitochondrial homeostasis regulation, the ischemia-reperfusion process exhibits distinct phasic alterations across the ischemic phase, early reperfusion, and late reperfusion stages. These dynamic changes are primarily characterized by metabolic reprogramming, excessive oxidative stress, mitochondrial dynamics imbalance, impaired mitophagy, loss of mitochondrial membrane integrity, and the release of mitochondria-derived damage-associated molecular patterns (DAMPs). Collectively, these events contribute to the initiation and progression of IRI and further promote dysregulated inflammatory responses. This review summarizes the phasic alterations of mitochondrial homeostasis and their interactions with immune-inflammatory pathways during hemorrhagic shock resuscitation. Understanding these temporal mechanisms may provide a rationale for stage-specific mitochondrial-targeted therapeutic strategies aimed at improving organ protection and modulating dysregulated immune-inflammatory responses.
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BibTeX
@article{zhou2026dynamic,
title = {{Dynamic changes of mitochondrial homeostasis and immune-inflammatory signaling during hemorrhagic shock resuscitation associated ischemia–reperfusion injury}},
author = {Yuting Zhou and Xiaoyu Zhang and Huifang Gao and Nan Ji and Bixi Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1910044},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1910044/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dynamic changes of mitochondrial homeostasis and immune-inflammatory signaling during hemorrhagic shock resuscitation associated ischemia–reperfusion injury
AU - Yuting Zhou
AU - Xiaoyu Zhang
AU - Huifang Gao
AU - Nan Ji
AU - Bixi Li
PY - 2026
DA - 2026/10/13
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1910044
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1910044/full
AB - Traumatic hemorrhagic shock is a common and life-threatening condition following severe trauma, characterized by reduced effective circulating blood volume and insufficient tissue perfusion, ultimately leading to an imbalance between oxygen supply and demand as well as progressive multi-organ dysfunction. Fluid resuscitation is essential for restoring hemodynamic stability; however, it may simultaneously trigger or aggravate ischemia-reperfusion injury (IRI). Emerging evidence suggests that disruption of mitochondrial homeostasis represents not only a critical cellular basis underlying organ injury during hemorrhagic shock resuscitation, but also an important driver of immune activation and inflammatory amplification. At the level of mitochondrial homeostasis regulation, the ischemia-reperfusion process exhibits distinct phasic alterations across the ischemic phase, early reperfusion, and late reperfusion stages. These dynamic changes are primarily characterized by metabolic reprogramming, excessive oxidative stress, mitochondrial dynamics imbalance, impaired mitophagy, loss of mitochondrial membrane integrity, and the release of mitochondria-derived damage-associated molecular patterns (DAMPs). Collectively, these events contribute to the initiation and progression of IRI and further promote dysregulated inflammatory responses. This review summarizes the phasic alterations of mitochondrial homeostasis and their interactions with immune-inflammatory pathways during hemorrhagic shock resuscitation. Understanding these temporal mechanisms may provide a rationale for stage-specific mitochondrial-targeted therapeutic strategies aimed at improving organ protection and modulating dysregulated immune-inflammatory responses.
SN - 1664-3224
ER -