Supplemental Materials Online Methods Animal model Mice with cardiomyocyte-restricted low-level overexpression of long-chain acyl-

Animal model Mice with cardiomyocyte-restricted low-level overexpression of long-chain acylCoA synthetase 1 (ACStg) and control littermates (WT) were originally on the FVB background1. We prepared a transgenic line on the C57BL6j background by backcrossing more than 8 generations. DRP1 floxed mice (Kind gift of Hiromi Sesaki, Johns Hopkins University, Baltimore MD) were used to generate cardiomyocyte-restricted heterozygous deletions of DRP1 (Mixed Background). Sod2 transgenic mice (FVB background) were a kind gift from Paul Epstein (University of Louisville, Louisville, KY) and Des1 +/mice (C57BL6 background) were a kind gift of Scott Summers (University of Utah, Salt Lake City, UT). Animals were studied in accordance with protocols approved by the Institutional Animal Care and Use Committees of the University Utah and the Carver College of Medicine of the University of Iowa. All mice were housed at 22°C with free access to water and food (standard chow diet) with a light cycle of 12h light and 12h dark.