Журнал "Гастроэнтерология" Том 59, №4, 2025

Актуальність. Мітохондрії, традиційно відомі як основні генератори АТФ, відіграють значно ширшу роль у високоспеціалізованих клітинах, зокрема в ацинарних клітинах підшлункової залози (АЦК). Вони є центральними регуляторами клітинного гомеостазу, кальцієвого обміну, окисно-відновного балансу, програмованої загибелі клітин та адаптації до стресу. Ці функції реалізуються не ізольовано, а в контексті складної міжорганелярної мережі. Особливості цих взаємодій набувають критичного значення при розвитку гострого панкреатиту (ГП) — тяжкої запальної патології з високим ризиком ускладнень і летальності. Сучасні дослідження приділяють все більше уваги концепції «мітохондріального хабу», що підкреслює інтегровану роль мітохондрій у клітинних процесах, а не лише їх функцію як ізольованих енергетичних одиниць. Метою цієї статті є аналіз та узагальнення даних щодо складної мережі міжорганелярних взаємодій мітохондрій з іншими клітинними структурами в ацинарних клітинах підшлункової залози з особливим акцентом на їхню роль у патогенезі гострого панкреатиту. Матеріали та методи. Стаття є оглядом сучасної наукової літератури, присвяченої мітохондріальним інтеграціям та їх ролі в патогенезі гострого панкреатиту. Джерела були відібрані з провідних медичних та біологічних баз даних, включаючи PubMed, Scopus та Google Scholar за 2019–2025 роки, а також до дослідження включені окремі фундаментальні публікації. Результати. Аналіз літератури підтвердив, що мітохондрії в АЦК функціонують як інтегрована частина багатокомпонентного «мітохондріального хабу», що включає динамічні взаємодії з ендоплазматичним ретикулумом, лізосомами, пероксисомами та іншими органелами. Показано, що порушення цих взаємодій є критичним фактором у розвитку ГП. Зокрема, дисфункція мітохондріально-ендоплазматичного контакту призводить до порушення кальцієвого гомеостазу та оксидативного стресу, що є ключовими подіями в ініціації панкреатиту. Також підкреслено роль порушень мітофагії та автофагії, які як взаємопов’язані процеси деградації мітохондрій та клітинних компонентів є вирішальними для підтримки клітинного здоров’я в АЦК, а їх порушення сприяє прогресуванню ГП. Виявлено, що активація прозапальних процесів в АЦК, індукована резистином, може бути пригнічена за допомогою α-ліпоєвої кислоти через активацію PPARγ, що посилює експресію HO-1 та каталази, знижуючи рівень активних форм кисню та ІЛ-6. Це свідчить про функціональну інтеграцію антиоксидантного захисту пероксисом і мітохондрій. Крім того, активація PPARγ також пригнічує NF-κB-залежну активацію альвеолярних макрофагів, знижуючи системне запалення, опосередковане екзосомами, що виділяються ушкодженими клітинами підшлункової залози. Висновки. Порушення динамічного балансу в «мітохондріальному хабі», особливо у взаємодії з ендоплазматичним ретикулумом, лізосомами та пероксисомами, є ключовим фактором у патогенезі гострого панкреатиту, сприяючи розвитку запалення, оксидативного стресу та клітинної смерті.

Background. Mitochondria, traditionally known as primary adenosine triphosphate generators, play a significantly greater role in highly specialized cells, particularly in pancreatic acinar cells (PACs). They are central regulators of cellular homeostasis, calcium metabolism, redox balance, programmed cell death, and stress adaptation. These functions are not implemented in isolation but within the context of a complex inter-organelle network. The specific characteristics of these interactions become critically important in the development of acute pancreatitis (AP), a severe inflammatory disorder with a high risk of complications and morta­lity. Contemporary research increasingly emphasizes the concept of the “mitochondrial hub,” which underscores the integrated role of mitochondria in cellular processes rather than just their function as isolated energetic units. The purpose of this article is to analyze and synthesize data regarding the complex network of inter-organelle interactions of mitochondria and other cellular structures in pancreatic acinar cells, with a particular focus on their role in the pathogenesis of acute pancreatitis. Materials and methods. This article is a review of current scientific literature on mitochondrial integrations and their role in the pathogenesis of acute pancreatitis. Sources were selected from leading medical and biological databases, inclu­ding PubMed, Scopus, and Google Scholar, for 2019–2025, as well as selected fundamental publications. Results. Literature analysis confirmed that mitochondria in PACs function as an integrated part of a multi-component “mitochondrial hub”, which involves dynamic interactions with the endoplasmic reticulum, lysosomes, peroxisomes, and other organelles. It was shown that disruptions of these interactions are critical factors in the development of AP. In particular, dysfunction of mitochondria-endoplasmic reticulum contact sites leads to impaired calcium homeostasis and oxidative stress, which are key events in the initiation of pancreatitis. The role of dysregulated mitophagy and autophagy, interconnected processes for the degradation of mitochondria and cellular components, was also highlighted as crucial for maintaining cellular health in PACs, and their disruption contributes to AP progression. It was found that the activation of pro-inflammatory processes in PACs, induced by resistin, can be suppressed by α-lipoic acid through the activation of PPARγ, which enhances the expression of HO-1 and catalase, thereby decreasing reactive oxygen species and IL-6 levels. This indicates a functional integration of peroxisomal and mitochondrial antioxidant defense. Furthermore, PPARγ activation also inhi­bits NF-κB-dependent activation of alveolar macrophages, redu­cing systemic inflammation mediated by exosomes released from damaged pancreatic cells. Conclusions. Disruption of the dynamic balance within the “mitochondrial hub,” especially in interaction with the endoplasmic reticulum, lysosomes, and peroxisomes, is a key factor in the pathogenesis of acute pancreatitis, contributing to the development of inflammation, oxidative stress, and cell death.

мітохондрії; ацинарні клітини; гострий панкреатит; міжорганелярні взаємодії

mitochondria; acinar cells; acute pancreatitis; inter-organelle interactions

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