Mitochondria are key to cellular energetics, metabolism, and signaling. Their dysfunction is linked to devastating diseases, including mitochondrial disorders, diabetes, neurodegenerative diseases, cardiac disorders, and cancer. Here, we present a knockout mouse model lacking the complex IV assembly factor SMIM20/MITRAC7. SMIM20-/- mice display cardiac pathology with reduced heart weight and cardiac output. Heart mitochondria present with reduced levels of complex IV associated with increased complex I activity, have altered fatty acid oxidation, and display elevated levels of ROS production. Interestingly, mutant mouse ventricular myocytes show unphysiological Ca2+ handling, which can be attributed to the increase in mitochondrial ROS production. Our study presents an example of a tissue-specific phenotype in the context of OXPHOS dysfunction. Moreover, our data suggest a link between complex IV dysfunction and Ca2+ handling at the endoplasmic reticulum through ROS signaling.

Bioanalytical Mass Spectrometry Group Max Planck Institute for Multidisciplinary Sciences 37077 Göttingen Germany

Bioanalytical Mass Spectrometry Group Max Planck Institute for Multidisciplinary Sciences 37077 Göttingen Germany; Department of Clinical Chemistry University Medical Center Göttingen 37075 Göttingen Germany

Czech Centre for Phenogenomics Institute of Molecular Genetics of the CAS 142 20 Prague Czech Republic

Department of Cardiovascular Physiology University Medical Center Göttingen 37073 Göttingen Germany

Department of Cellular Biochemistry University Medical Center Göttingen 37073 Göttingen Germany

Department of Cellular Biochemistry University Medical Center Göttingen 37073 Göttingen Germany; German Center for Child and Adolescent Health 37075 Göttingen Germany

Department of Cellular Biochemistry University Medical Center Göttingen 37073 Göttingen Germany; German Center for Child and Adolescent Health University of Göttingen 37075 Göttingen Germany; Max Planck Institute for Multidisciplinary Science 37077 Göttingen Germany; Fraunhofer Institute for Translational Medicine and Pharmacology Translational Neuroinflammation and Automated Microscopy 37075 Göttingen Germany

Institute of Pharmacology and Toxicology University Medical Center Göttingen Georg August University Göttingen 37075 Göttingen Germany; German Center for Cardiovascular Research Partner Site Göttingen 37075 Göttingen Germany

Institute of Pharmacology and Toxicology University Medical Center Göttingen Georg August University Göttingen 37075 Göttingen Germany; German Center for Cardiovascular Research University of Göttingen 37075 Göttingen Germany

Citace poskytuje Crossref.org