Cyclophilin D and myocardial ischemia–reperfusion injury: A fresh perspective. (January 2015)

• Record Type: Journal Article
• Authors: Alam, Muhammad Rizwan; Baetz, Delphine; Ovize, Michel
• Is Part Of: Journal of molecular and cellular cardiology. Volume 78(2015:Jan.)
• Page Start: 80
• Page End: 89
• Publication Date: 2015-01
• Subjects: ANT adenine nucleotide translocator -- ATP adenosine triphosphate -- ATP5G ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9) -- BAK BCL2-antagonist/killer -- BAX BCL2-associated X protein -- BCL-2 B cell lymphoma protein 2 -- C1QBP complement 1q-binding protein -- CGP37157 7-Chloro-5-(2-chlorophenyl)-1, 5-dihydro-4, 1-benzothiazepin-2(3H)-one -- CKMT1 creatine kinase mitochondrial 1 -- CsA cyclosporin A -- CSMDHs calcium-sensitive matrix dehydrogenases -- CypA cyclophilin A -- CypD cyclophilin D -- DnaJC15 DnaJ (Hsp40) homolog, subfamily C, member 15 -- EMRE essential MCU regulator -- ER endoplasmic reticulum -- ERK2 extracellular regulated kinase 2 -- GRP75 Glucose regulated protein 75 -- GSK3β glycogen synthase kinase 3β -- HK1/2 hexokinase 1/2 -- HSP60/90 heat shock protein 60/90 -- IMM inner mitochondrial membrane -- IP3 inositol 1, 4, 5 trisphosphate -- IP3R1 inositol 1, 4, 5 trisphosphate receptor type 1 -- IR ischemia reperfusion -- LV left ventricle -- KO Knockout -- MAMs mitochondria-associated membranes -- MCU mitochondrial calcium uniporter -- MI myocardial infarction -- MICU1 mitochondrial calcium uptake 1 -- MLKL mixed lineage kinase domain-like protein -- mPTP mitochondrial permeability transition pore -- MST1 mammalian sterile 20-like kinase 1 -- mΔΨ mitochondrial membrane potential -- NAD+ nicotinamide adenine dinucleotide oxidized -- NADH nicotinamide adenine dinucleotide reduced -- NCLX sodium calcium lithium exchanger -- NIM811 N-methyl-4-isoleucine cyclosporine -- OSCP oligomycin-sensitivity conferring protein -- PAGE polyacrylamide gel electrophoresis -- Pi inorganic phosphate -- PiC mitochondrial phosphate carrier -- PostC post-conditioning -- PPIase peptidyl-prolyl cis-trans isomerase -- PPIF peptide-prolyl isomerase F -- PreC pre-conditioning -- PT mitochondrial permeability transition -- PTMs post-translational modifications -- RIPK1 receptor-interacting protein kinase 1 -- RIPK3 receptor-interacting protein kinase 3 -- ROS reactive oxygen species -- SfA sanglifehrin A -- SERCA sarco/endoplasmic reticulum Ca2 +-ATPase -- siRNA small interfering RNA -- SIRT3 sirtuin 3 -- SNO S-nitrosylation -- STEMI ST segment elevation myocardial infarction -- STAT3 signal transducer and activator of transcription 3 -- TRAP1 tumor necrosis factor receptor-associated protein 1 -- TSPO translocator protein -- VDAC voltage-dependent anion channel; Ischemia–reperfusion -- Cyclophilin D -- Mitochondrial permeability transition pore -- Cell death -- Necrosis; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2014.09.026
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Reperfusion is characterized by a deregulation of ion homeostasis and generation of reactive oxygen species that enhance the ischemia-related tissue damage culminating in cell death. The mitochondrial permeability transition pore (mPTP) has been established as an important mediator of ischemia–reperfusion (IR)-induced necrotic cell death. Although a handful of proteins have been proposed to contribute in mPTP induction, cyclophilin D (CypD) remains its only bona fide regulatory component. In this review we summarize existing knowledge on the involvement of CypD in mPTP formation in general and its relevance to cardiac IR injury in specific. Moreover, we provide insights of recent advancements on additional functions of CypD depending on its interaction partners and post-translational modifications. Finally we emphasize the therapeutic strategies targeting CypD in myocardial IR injury. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". Highlights: Myocardial ischemia–reperfusion injury triggers mPTP opening. Cyclophilin D is the bona fide regulatory component of the mPTP. Cyclophilin D inhibition is a viable therapeutic strategy for reperfusion injury.