Ablation of the stress protease OMA1 protects against heart failure

Heart failure (HF) is a major health and economic burden in developed countries. It has been proposed that the pathogenesis of HF may involve the action of mitochondria. Here we evaluate three different models of HF: tachycardiomyopathy, HF with preserved left ventricular (LV) ejection fraction, and LV myocardial ischemia and hypertrophy. Regardless of whether LVEF is preserved or reduced, our results indicate that the three models share common molecular features: an increase in mitochondrial ROS, followed by ultrastructural alterations in the mitochondrial cristae and loss of mitochondrial integrity that lead to cardiomyocyte death. We show that the ablation of the mitochondrial protease OMA1 averts cardiomyocyte death in all three experimental HF models, and thus, plays a direct role in cardiomyocyte protection. This finding identifies OMA1 as a potential target for preventing the progression of myocardial damage in HF associated to a variety of etiologies. Overall design: Transcriptome analysis of 12-week-old wild type mice versus OMA1 KO mice under control (non-treated) or treated with Isoproterenol chronically (implanted minipumps) for 7 days in heart tissue. The nuclear genetic background for both genotypes is C57BL/6JOlaHsd.

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Acin-Perez R, Lechuga-Vieco AV, Del Mar Muñoz M, Nieto-Arellano R, Torroja C, Sánchez-Cabo F, Jiménez C, González-Guerra A, Carrascoso I, Benincá C, Quiros PM, López-Otín C, Castellano JM, Ruíz-Cabello J, Jiménez-Borreguero LJ, Enríquez JA