OMA1-mediated integrated stress response protects against ferroptosis in mitochondrial cardiomyopathy
Sofia Ahola, Pablo Rivera-Mejías, Steffen Hermans, Srikanth Chandragiri, Patrick Giavalisco, Hendrik Nolte, Thomas Langer
Abstract
mice aggravates cardiomyopathy. ISR inhibition impairs the cardiac glutathione metabolism, limits the selenium-dependent accumulation of the glutathione peroxidase Gpx4, and increases lipid peroxidation in the heart, ultimately culminating in ferroptosis. Our results demonstrate a protective role of the Oma1-Dele1-mediated ISR in mitochondrial cardiomyopathy and link ferroptosis to OXPHOS deficiency and mitochondrial disease.
Topics & Concepts
MitochondrionOxidative stressCardiomyopathyDNAJA3BiologyCell biologymitochondrial fusionOxidative phosphorylationMitochondrial DNAInternal medicineHeart failureEndocrinologyMedicineBiochemistryGeneMitochondrial Function and PathologyRNA modifications and cancerATP Synthase and ATPases Research