Supplementary Materials

The PDF file includes:

• Materials and Methods
• Fig. S1. Dsg2^mut/mut mice display ECG abnormalities and myocardial injury in response to endurance exercise.
• Fig. S2. CAPN1 activation and cell death in response to Ca²⁺ overload.
• Fig. S3. CAPN1 inhibition in HL-1 cells by PD150606.
• Fig. S4. CytC in Dsg2^mut/mut mice and posttranslational modifications of AIF.
• Fig. S5. AIF localization in ACM patient myocardium.
• Fig. S6. Dsg2^mut/mut mice display reduced COX IV abundance and aberrant myocardial localization.
• Fig. S7. Labeled cysteines and DNA gel electrophoresis.
• Fig. S8. HSP70 and PPIA abundance in ACM myocytes.
• Fig. S9. Increased AIF nuclear localization and nuclear loss of HMGB1 in ACM ES-CMs.
• Fig. S10. Graphical abstract of exercise-induced, CAPN1/PPIA-mediated AIF-nuclear import in ACM.
• Table S1. Echocardiographic and electrocardiographic indices from exercised WT and Dsg2^mut/mut mice.
• Table S2. Desmosomal gene variants in patients with ACM.
• Table S3. Clinical characteristics and AIF pathology scores of patients with ACM.
• Legend for data file S1

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Other Supplementary Material for this manuscript includes the following:

• Data file S1 (Microsoft Excel format). Raw data.