In the field of perioperative medicine, organ injury has significantly impacted surgical outcomes, primarily driven by ischemia-reperfusion injury, oxidative stress, and dysregulated inflammation. Central to these pathological processes is mitochondrial dysfunction, which hinders cellular bioenergetics and exacerbates immunological disturbances. During surgical interventions, damaged mitochondria emit damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), reactive oxygen species (ROS), and cardiolipin. These molecules activate the innate immune response through pathways like cGAS-STING and NLRP3 inflammasomes, corresponding with macrophage and neutrophil activation and subsequent exacerbation of inflammatory pathways. Current strategies to address these complex interactions remain limited and warrant further exploration.

This Research Topic seeks to advance mitochondrial-centric strategies for perioperative organ protection. We emphasize mechanistic studies elucidating mitochondrial damage in immune dysregulation (e.g., trained immunity, cytokine storms) and translational innovations—including mitochondrial transplantation, nanoparticle-mediated drug delivery, and biomarker-driven therapies—to restore immune homeostasis. By bridging mitochondrial biology and immunology, this Topic aims to pioneer precision interventions that convert inflammatory injury into regenerative recovery.

This Research Topic invites contributions elucidating mitochondrial-immune interactions in perioperative organ injury and their therapeutic modulation. Key themes include:

1. Mechanistic Links Between Mitochondrial Damage and Immune Dysregulation

- Molecular pathways through which mitochondrial dysfunction (e.g., mtDNA release, oxidative stress) activates innate immunity (cGAS-STING, NLRP3 inflammasomes) and disrupts adaptive immune responses (T-cell exhaustion, macrophage polarization).

- Metabolic reprogramming of immune cells (e.g., glycolysis vs. oxidative phosphorylation) during ischemia-reperfusion injury or sepsis.

2. Precision Therapeutics Targeting Mitochondria-Immune Crosstalk

- Development of mitochondria-specific nanomedicines (e.g., ROS-responsive nanoparticles, mitophagy enhancers) to modulate inflammatory pathways or promote tissue repair.

- Mitochondrial transplantation and bioengineered mitochondria as strategies to restore cellular energetics and immune homeostasis.

- Synergistic approaches combining immunotherapies (e.g., checkpoint inhibitors) with mitochondrial protectants (e.g., SS-31 peptide) in perioperative settings.

3. Translational Biomarkers and Clinical Integration

- Identification of mitochondrial-immune biomarkers (e.g., circulating mtDNA, mitophagy flux) for early diagnosis and prognosis of organ dysfunction.

- Preclinical validation of combinatorial therapies (e.g., mitochondrial antioxidants + anti-IL-1β agents) using organoids or large-animal models.

4. Innovative Clinical Strategies

- Trials evaluating mitochondrial-targeted interventions (e.g., MitoQ, engineered CAR-T/NK cells with enhanced mitochondrial fitness) for organ protection.

- Biomarker-guided protocols to personalize immunomodulatory therapies in high-risk surgical patients.

Submissions must emphasize mechanistic depth or translational relevance. Purely computational studies lacking experimental validation are excluded.

Are you interested in contributing a manuscript to this Research Topic?

Immunomodulatory Strategies in Perioperative Organ Protection: From Mitochondrial Dysfunction to Clinical Applications