REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1575242
Cyclophilin D (PPIF) and MPTP in Hepatic Ischemia-Reperfusion Injury: Insights into Mechanisms
Provisionally accepted
- 1Shenzhen Technology University, Shenzhen, China
- 2Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan Province, China
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Hepatic ischemia-reperfusion injury (HIRI) is a major complication in liver transplantation, hepatic surgeries, and shock-induced acute liver failure. This injury is characterized by mitochondrial dysfunction, oxidative stress, and calcium overload, with the mitochondrial permeability transition pore (mPTP) playing a pivotal role in mediating hepatocyte death. Cyclophilin D (CypD), a key regulator of mPTP opening, has long been associated with the exacerbation of HIRI. However, recent research has uncovered a protective aspect of CypD, revealing that it can regulate intermittent or "flickering" mPTP openings to control calcium overload, preserve mitochondrial integrity, and mitigate damage during ischemic stress. This review highlights the dual role of CypD in regulating mitochondrial damage through mPTP dynamics and its complex interplay with autophagy, specifically mitophagy, in liver injury. We also explore the emerging pharmacological and genetic approaches targeting PPIF, offering potential avenues for mitigating liver injury in clinical settings. This review integrates recent findings on PPIF's role in mPTP regulation, inflammation, autophagy, and mitophagy, proposing a nuanced view of its therapeutic potential in managing hepatic ischemia-reperfusion injury.
Keywords: Cyclophilin D (CypD), MPTP, Hepatic ischemia-reperfusion injury, mechanisms, mitophagy, Inflammatary disease, calcium overload
Received: 12 Feb 2025; Accepted: 16 Jun 2025.
Copyright: © 2025 Liu, Wu, Lin, Ma, Wang and ZENG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jingxin Liu, Shenzhen Technology University, Shenzhen, China
Kai Wang, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
BIN ZENG, Shenzhen Technology University, Shenzhen, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.