Tangled contacts: mitochondrial interactions with cellular organelles in acute pancreatitis

Mitochondria in pancreatic acinar cells function as central hubs integrating calcium signaling, ATP production, redox balance, autophagy, secretion, and cell-death regulation through dynamic interactions with other organelles.

To summarize current evidence on mitochondria-organelle interactions in pancreatic acinar cells and their relevance to acute pancreatitis.

We performed a narrative review of experimental and translational studies addressing mitochondrial interactions with the endoplasmic reticulum, lysosomes, autophagosomes, peroxisomes, the cytoskeleton, plasma membrane, nucleus, lipid droplets, and secretory granules in pancreatic acinar cells and experimental acute pancreatitis.

Mitochondria-endoplasmic reticulum contacts emerged as major determinants of pathological Ca²⁺ transfer, mitochondrial depolarization, and ATP depletion. Impaired crosstalk with lysosomes and autophagosomes disrupted mitophagy and favored the persistence of dysfunctional mitochondria, defective vacuolar processing, and inflammatory amplification. Altered functional coupling with peroxisomes and lipid droplets intensified oxidative stress, fatty-acid disequilibrium, and lipotoxic injury, particularly in metabolically unfavorable settings. Disturbed interactions with the cytoskeleton and plasma membrane impaired mitochondrial positioning, local Ca²⁺ buffering, and the spatial organization of stimulus-secretion coupling. Mitochondria-to-nucleus signaling promoted stress-responsive and proinflammatory transcriptional programs, while mitochondrial failure in the apical secretory region indirectly facilitated defective exocytosis and premature zymogen activation. Collectively, these alterations shifted acinar cells from adaptive stress responses toward necrosis, local pancreatic damage, systemic inflammation, and organ failure.

Mitochondria-associated inter-organellar networks are integral to acinar-cell homeostasis and critically influence the initiation and progression of acute pancreatitis. Their selective stabilization may represent a mechanistically grounded therapeutic direction.