Title:Cyclophilin D-mediated Mitochondrial Permeability Transition Regulates Mitochondrial
Function
Volume: 29
Issue: 8
Author(s): Shaoyun Zhou, Qinwei Yu, Luyong Zhang and Zhenzhou Jiang*
Affiliation:
- New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, Jiangsu Key Laboratory of Druggability
of Biopharmaceuticals, China Pharmaceutical University, Nanjing, 210009, China
- Key Laboratory of Drug Quality Control
and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, 210009, China
Keywords:
Mitochondria, mitochondrial permeability transition pore, cyclophilin D, mechanisms, reactive oxygen species, cell death.
Abstract:
Background: Mitochondria are multifunctional organelles, which participate in biochemical processes.
Mitochondria act as primary energy producers and biosynthetic centers of cells, which are involved in oxidative
stress responses and cell signaling transduction. Among numerous potential mechanisms of mitochondrial
dysfunction, the opening of the mitochondrial permeability transition pore (mPTP) is a major determinant of mitochondrial
dysfunction to induce cellular damage or death. A plenty of studies have provided evidence that the
abnormal opening of mPTP induces the loss of mitochondrial membrane potential, the impairment calcium
homeostasis and the decrease of ATP production. Cyclophilin D (CypD), localized in the mitochondrial transition
pore, is a mitochondrial chaperone that has been regarded as a prominent mediator of mPTP.
Methods: This review describes the relationship between CypD, mPTP, and CypD-mPTP inhibitors through
systematic investigation of recent relevant literature.
Results: Here, we have highlighted that inhibiting the activity of CypD protects models of some diseases, including
ischaemia/reperfusion injury (IRI), neurodegenerative disorders and so on. Knockdown studies have demonstrated
that CypD possibly is mediated by its peptidyl-prolyl cis-trans isomerase activity, while the primary
targets of CypD remain obscure. The target of CypD-mPTP inhibitor can alleviate mPTP opening-induced cell
death. The present review is focused on the role of CypD as a prominent mediator of the mPTP, further providing
insight into the physiological function of mPTP and its regulation by CypD.
Conclusion: Blocking the opening of mPTP by inhibiting CypD might be a new promising approach for suppressing
cell death, which will suggest novel therapeutic approaches for mitochondria-related diseases.
