Combination of common mtDNA variants results in mitochondrial dysfunction and a connective tissue dysregulation
Year: 2022
Type: article
Abstract: Mitochondrial dysfunction is associated with a range of clinical manifestations including neuropsychiatric and metabolic disorder. Here, we reanalyzed a family with an L-Histidine Decarboxylase (HDC) variant previously linked to Tourette syndrome but with associated connective tissue and metabolic features of unknown etiology. We identified a mitochondrial haplogroup J-defining mutation on the haplogroup H background that functionally interacts with the L-Histidine Decarboxylase variant via calcium homeostasis. Our findings establish how a common mtDNA variant on a different mtDNA background can result in mitochondrial dysfunction, demonstrate a role for histaminergic signaling in modifying mitochondrial phenotypes, and link mitochondria dysfunction to connective tissue phenotypes.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: U.S. Department of Defense, University of Pennsylvania, Deutsche Forschungsgemeinschaft, National Institutes of Health, National Institute of Mental Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1433873921, G21146293, G2262409748, G23045533, Role of Histone and Histone-like Mutations in the Oncogenesis of Human Cancers, G3865632432, G3979633579, G4119534169, A MITOCHONDRIAL-INTERNEURONAL HYPOTHESIS OF AUTISM, COVID-19 SARS-COV-2 PROPAGATION AND PATHOLOGY AND MITOCHONDRIAL GENETICS, G5407178560, G5850682332, G6502886799, Mitochondrial Inborn Errors in Metabolism, Mouse models for mitochondrial disorders caused by mutations in mtDNA, POWERING UP MITOCHONDRIAL FUNCTIONS TO TREAT MITOCHONDRIAL DISEASE, G8390724461, Viral modulation of epitranscriptomic mechanisms
OpenAlex ID: W4308146202