Cyclophilin D-mediated Mitochondrial Permeability Transition Regulates Mitochondrial Function
- PMID: 36915987
- DOI: 10.2174/1381612829666230313111314
Cyclophilin D-mediated Mitochondrial Permeability Transition Regulates Mitochondrial Function
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.
Keywords: Mitochondria; cell death; cyclophilin D; mechanisms; mitochondrial permeability transition pore; reactive oxygen species.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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