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SMIM20 promotes complex IV biogenesis and Ca2+ Signalling in mice heart

GSE282428 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/04/04 Platform GPL24247
Summary
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 novel 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 a new 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.
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Also filed as BioProject PRJNA1188571 and SRA study SRP546497. Searching any of these in the dataset finder brings you back here.

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