Mitochondrial dysfunction as a bridge to pathology in acute pancreatitis: From molecular insights to novel therapeutic strategies.

Acute pancreatitis (AP) is a life-threatening inflammatory condition triggered by the premature activation of trypsin. The limited understanding of its underlying pathophysiology remains a key obstacle to the development of targeted therapies. Mounting evidence now underscores mitochondrial dysfunction as a critical pathogenic driver in AP. Cellular mitochondrial dysfunction often precedes both cytokine release and trypsin activation, potentially serving as a primary initiator in the development and advancement of AP. Mitochondrial dysfunction is associated with calcium overload, inflammatory reactions, mitochondrial permeability transition pore opening, mitophagy damage, and other potential pathogenesis of pancreatic cell injury. Elucidating the impact of mitochondrial injury in AP may facilitate the development of innovative treatment approaches. This review provides a comprehensive and systematic analysis of the pivotal role of mitochondria in regulating pancreatic homeostasis, while evaluating emerging therapeutic strategies aimed at mitigating mitochondrial dysfunction. By integrating cutting-edge research findings, this work highlights the translational potential of these advancements in redefining diagnostic frameworks and optimizing therapeutic approaches for the management of AP.