• Geoffrey Teixeira, Maryline Abrial, Karine Portier, Pascal Chiari, Elisabeth Couture-Lepetit, Yves Tourneur, Michel Ovize, and Abdallah Gharib.
• INSERM UMR 1060, CarMeN, F-69373, Lyon, France.
• J. Mol. Cell. Cardiol. 2013 Mar 1;56:55-62.

AbstractReperfusion of the heart after an ischemic event leads to the opening of a nonspecific pore in the inner mitochondrial membrane, the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP opening is an effective strategy to prevent cardiomyocyte death. The matrix protein cyclophilin-D (CypD) is the best-known regulator of mPTP opening. In this study we confirmed that preconditioning and postconditioning with CypD inhibitor cyclosporin-A (CsA) reduced cell death after hypoxia-reoxygenation (H/R) in wild-type (WT) cardiomyocytes and HL-1 mouse cardiac cell line as measured by nuclear staining with propidium iodide. The complex I inhibitor rotenone (Rot), alone, had no effect on HL-1 and WT cardiomyocyte death after H/R, but enhanced the native protection of CypD-knocked-out (CypD KO) cardiomyocytes. Reduction of cell death was associated with a delay of mPTP opening challenged by H/R and observed by the calcein loading CoCl(2)-quenching technique. Simultaneous inhibition of complex I and CypD increased in a synergistic manner the calcium retention capacity in permeabilized cardiomyocytes and cardiac mitochondria. These results demonstrated that protection by complex I inhibition was CypD dependent.Copyright © 2013 Elsevier Ltd. All rights reserved.

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