Exercise triggers CAPN1-mediated AIF truncation, inducing myocyte cell death in arrhythmogenic cardiomyopathy

Authors: Stephen P. Chelko, Gizem Keceli, Andrea Carpi, Nunzianna Doti, Jacopo Agrimi, Angeliki Asimaki, Carlos Bueno‐Betí, Matthew Miyamoto, Nuria Amat-Codina, Djahida Bedja, An‐Chi Wei, Brittney Murray, Crystal Tichnell, Chulan Kwon, Hugh Calkins, Cynthia A. James, Brian O’Rourke, Marc K. Halushka, Edon Melloni, Jeffrey E. Saffitz, Daniel P. Judge, Menotti Ruvo, Richard N. Kitsis, Peter Andersen, Fabio Di Lisa, Nazareno Paolocci - Science Translational Medicine 2021 cited by 91

ES-CMs with an AIF-mimetic peptide, mirroring the cyclophilin-A (PPIA) binding site of AIF, blocked PPIA-mediated AIF-nuclear translocation, and reduced both apoptosis and necrosis. Thus, preventing CAPN1-induced AIF-truncation or barring binding of AIF to the nuclear chaperone, PPIA, may avert myocyte death and, ultimately, disease progression to heart failure in ACM and likely other forms of cardiomyopathies.