Cyclophilin D Modulates Mitochondrial F0F1-ATP Synthase by Interacting with the Lateral Stalk of the Complex

• DOI: 10.1074/jbc.m109.020115
• Publication Date: 2009-09-30T01:24:44Z
• Authors: Valentina Giorgio; Elena Bisetto; Maria Eugenia Sor...; Federica Dabbeni-...; Emy Basso; Valeria Petronilli; Michael A. Forte; Paolo Bernardi; Giovanna Lippe
• Keywords: Submitochondrial particle; Inhibitor protein; Cyclophilin; V-ATPase; Chemiosmosis; Adenosine triphosphate; F-ATPase

Blue native gel electrophoresis purification and immunoprecipitation of F(0)F(1)-ATP synthase from bovine heart mitochondria revealed that cyclophilin (CyP) D associates to the complex. Treatment intact with membrane-permeable bifunctional reagent dimethyl 3,3-dithiobis-propionimidate (DTBP) cross-linked CyPD lateral stalk ATP synthase, whereas no interactions F(1) sector subunits, natural inhibitor protein IF1, ATP/ADP carrier were observed. The synthase-CyPD have functional consequences on enzyme catalysis are modulated by phosphate (increased binding decreased activity) cyclosporin (Cs) A (decreased increased activity). MgATP submitochondrial particles or CsA displaced membranes activated both hydrolysis synthesis sustained enzyme. No effect was detected in CyPD-null mitochondria, which displayed a higher specific activity than wild-type mitochondria. Modulation appears be independent whose association not affected treatment. These findings demonstrate modulates