Three lines of mitochondrial defense in acute pancreatitis: bioenergetics, redox balance, and permeability transition pore inhibition

Mitochondrial dysfunction plays a central role in the pathogenesis of acute pancreatitis (AP), leading to impaired adenosine triphosphate (ATP) production, loss of mitochondrial membrane potential (m), excessive reactive oxygen species (ROS) formation, and opening of the mitochondrial permeability transition pore (mPTP), which drives acinar cell necrosis and systemic inflammation. These mechanisms highlight mitochondria as a promising therapeutic target. The purpose was to summarize experimental strategies for mitochondria-targeted therapy in AP, focusing on three major aspects: support of bioenergetic homeostasis, antioxidant action, and inhibition of mPTP ope­ning. A structured analysis of original experimental studies from PubMed, Scopus, and Google Scholar was conducted. Studies examined the effects of mitochondria-targeted agents on ATP synthesis, m stabilization, oxidative stress, regulatory pathways (SIRT1, Nrf2, HtrA2, PGC-1), necrosis, inflammatory response, and mPTP regulation in AP models. Energy-supporting agents (e.g., carnitine, NMN, elamipretide, coenzyme Q10, melatonin) enhanced mitochondrial function and acinar cell viability. Antioxidants (e.g., curcumin, hydroxytyrosol, quercetin, astragaloside IV, tiron) reduced ROS-mediated injury via Nrf2/ARE pathway activation. mPTP inhibitors (cyclosporine, SS-31) preserved m and reduced necrosis. MitoTEMPO and hydrogen-rich saline primarily acted as mitochondria-targeted antioxidants, reducing ROS levels, which secondarily resulted in suppression of inflammasome activation. In contrast, MitoQ and SkQ1 showed unfavorable or inconsistent results. Mitochondria-targeted therapy is a promising approach to experimental AP treatment. Agents that support mitochondrial energetics, reduce oxidative stress, and inhibit mPTP opening offer cytoprotective benefits and may improve disease outcomes. Future research should focus on clinical validation and combined therapeutic strategies.