Cyclophilin D in mitochondrial pathophysiology

• Published in: Biochimica et biophysica acta Vol. 1797; no. 6-7; pp. 1113 - 1118
• Main Authors: Giorgio, Valentina, Soriano, Maria Eugenia, Basso, Emy, Bisetto, Elena, Lippe, Giovanna, Forte, Michael A., Bernardi, Paolo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2010
• Subjects: Animals; ATP synthase; Calcineurin - metabolism; Cyclophilin; Cyclophilins - deficiency; Cyclophilins - genetics; Cyclophilins - metabolism; Cyclosporin A; Cyclosporine - metabolism; Disease Models, Animal; Humans; Mice; Mice, Knockout; Mitochondria; Mitochondria - metabolism; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Permeability Transition Pore; Mitochondrial Proton-Translocating ATPases - metabolism; Models, Biological; Peptidyl-Prolyl Isomerase F; Permeability transition; Protein Interaction Domains and Motifs; Cs; Mitochondria; ATP synthase; Permeability transition; FKBP; Cyclophilin; ANT; PPIase; CyP; Cyclosporin A; PTP
• ISSN: 0005-2728; 0006-3002; 1879-2650
• DOI: 10.1016/j.bbabio.2009.12.006

Cyclophilins are a family of peptidyl-prolyl cis–trans isomerases whose enzymatic activity can be inhibited by cyclosporin A. Sixteen cyclophilins have been identified in humans, and cyclophilin D is a unique isoform that is imported into the mitochondrial matrix. Here we shall (i) review the best characterized functions of cyclophilin D in mitochondria, i.e. regulation of the permeability transition pore, an inner membrane channel that plays an important role in the execution of cell death; (ii) highlight new regulatory interactions that are emerging in the literature, including the modulation of the mitochondrial F1FO ATP synthase through an interaction with the lateral stalk of the enzyme complex; and (iii) discuss diseases where cyclophilin D plays a pathogenetic role that makes it a suitable target for pharmacologic intervention.