SMIM20 promotes complex IV biogenesis and Ca2+ signaling in mice heart
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
40402744
DOI
10.1016/j.celrep.2025.115723
PII: S2211-1247(25)00494-2
Knihovny.cz E-resources
- Keywords
- CP: Cell biology, CP: Molecular biology, OXPHOS, assembly factor, cytochrome c oxidase, mitochondria, mitochondrial disease,
- MeSH
- Endoplasmic Reticulum metabolism MeSH
- Myocytes, Cardiac metabolism MeSH
- Membrane Proteins * metabolism genetics MeSH
- Mitochondrial Proteins * metabolism genetics MeSH
- Myocardium * metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Oxidative Phosphorylation MeSH
- Reactive Oxygen Species metabolism MeSH
- Electron Transport Complex IV * metabolism MeSH
- Mitochondria, Heart metabolism MeSH
- Calcium metabolism MeSH
- Calcium Signaling * MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Membrane Proteins * MeSH
- Mitochondrial Proteins * MeSH
- Zebrafish Proteins MeSH
- Reactive Oxygen Species MeSH
- Electron Transport Complex IV * MeSH
- smim20 protein, zebrafish MeSH Browser
- Calcium MeSH
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.
Department of Cardiovascular Physiology University Medical Center Göttingen 37073 Göttingen Germany
Department of Cellular Biochemistry University Medical Center Göttingen 37073 Göttingen Germany
References provided by Crossref.org
