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Purpose <p>To synthesize experimental and clinical evidence on mitochondria-targeted strategies in acute pancreatitis (AP) and evaluate the potential of interventions that preserve or restore mitochondrial function to reduce pancreatic injury and systemic complications.</p> Methods <p>We conducted a narrative review of PubMed, Scopus, and Google Scholar through 2025, focusing on preclinical and clinical studies assessing mitochondrial structure/function or interventions targeting mitochondrial pathways in AP. Outcomes included mitochondrial membrane potential (ΔΨm), ATP content, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, calcium handling, mitophagy and biogenesis markers (e.g., PINK1/Parkin, PGC-1α/NRF1/TFAM), and cell death, with selective inclusion of early clinical data.</p> Results <p>Multiple mitochondria-targeted strategies consistently mitigated pancreatic injury in cellular and animal models of AP. Bioenergetic support with L-carnitine, NAD<sup>+</sup> precursors, coenzyme Q10, deoxyarbutin, and melatonin restored ATP levels and stabilized ΔΨm, while ΔΨm preservation and mPTP modulation by irisin, cyclosporine/NIM811, and TRO40303 limited necrosis. Redox modulation using Nrf2 activators (sulforaphane, paeonol, hydroxytyrosol, curcumin), MitoTEMPO, tiron, and hydrogen-rich saline reduced mtROS production and inflammasome activation, although MitoQ and SkQ1 showed mixed or adverse effects. Restraining pathological calcium flux through ruthenium red–mediated MCU inhibition prevented Ca<sup>2+</sup>-induced mitochondrial collapse, and enhancement of organelle quality control via rapamycin, urolithin A, selenium, and trehalose promoted mitophagy and mitochondrial biogenesis. Several interventions also attenuated extra-pancreatic organ injury. However, evidence remains predominantly preclinical, heterogeneous, and limited by challenges in targeted delivery across the hemato-pancreatic barrier.</p> Conclusion <p>Mitochondria-targeted therapies offer a mechanistically grounded strategy to reduce AP severity. Key priorities include optimizing pharmacokinetics and targeting, harmonizing experimental and clinical endpoints, and conducting rigorously designed clinical trials to translate preclinical benefits into meaningful patient outcomes.</p>

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Beyond Supportive Care: Mitochondria as a Strategic Therapeutic Avenue in Acute Pancreatitis

  • 期刊论文

  • 发表日期：

    2026年3月19日

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  • Serge Chooklin,
  • Serhii Chuklin

摘要

Purpose

To synthesize experimental and clinical evidence on mitochondria-targeted strategies in acute pancreatitis (AP) and evaluate the potential of interventions that preserve or restore mitochondrial function to reduce pancreatic injury and systemic complications.

Methods

We conducted a narrative review of PubMed, Scopus, and Google Scholar through 2025, focusing on preclinical and clinical studies assessing mitochondrial structure/function or interventions targeting mitochondrial pathways in AP. Outcomes included mitochondrial membrane potential (ΔΨm), ATP content, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, calcium handling, mitophagy and biogenesis markers (e.g., PINK1/Parkin, PGC-1α/NRF1/TFAM), and cell death, with selective inclusion of early clinical data.

Results

Multiple mitochondria-targeted strategies consistently mitigated pancreatic injury in cellular and animal models of AP. Bioenergetic support with L-carnitine, NAD+ precursors, coenzyme Q10, deoxyarbutin, and melatonin restored ATP levels and stabilized ΔΨm, while ΔΨm preservation and mPTP modulation by irisin, cyclosporine/NIM811, and TRO40303 limited necrosis. Redox modulation using Nrf2 activators (sulforaphane, paeonol, hydroxytyrosol, curcumin), MitoTEMPO, tiron, and hydrogen-rich saline reduced mtROS production and inflammasome activation, although MitoQ and SkQ1 showed mixed or adverse effects. Restraining pathological calcium flux through ruthenium red–mediated MCU inhibition prevented Ca2+-induced mitochondrial collapse, and enhancement of organelle quality control via rapamycin, urolithin A, selenium, and trehalose promoted mitophagy and mitochondrial biogenesis. Several interventions also attenuated extra-pancreatic organ injury. However, evidence remains predominantly preclinical, heterogeneous, and limited by challenges in targeted delivery across the hemato-pancreatic barrier.

Conclusion

Mitochondria-targeted therapies offer a mechanistically grounded strategy to reduce AP severity. Key priorities include optimizing pharmacokinetics and targeting, harmonizing experimental and clinical endpoints, and conducting rigorously designed clinical trials to translate preclinical benefits into meaningful patient outcomes.