| 66826 |
Q91WF0 |
TAZ_MOUSE |
Tafazzin (Taz) (EC 2.3.1.-) |
DISRUPTION PHENOTYPE |
Impaired cardiolipin (CL) metabolism with accumulation of monolysocardiolipin (MLCL) and reduction of mature CL in embryonic stem cells, male sterility, reduced testis size and disruption in progression of spermatocytes through meiosis (PubMed:26114544). Spermatocytes fail to progress past the pachytene stage of meiosis and have higher levels of DNA double strand damage and increased levels of endogenous retrotransposon activity (PubMed:26114544). RNAi-mediated knockdown results in prenatal and perinatal lethality, impaired CL metabolism resulting in absence of tetralineoyl-cardiolipin and accumulation of MLCL in cardiac and skeletal muscle, abnormal ultrastructure of mitochondria and mitochondrial-associated membranes, impaired skeletal muscle contractile properties, early diastolic dysfunction, and cardiac abnormalities such as myocardial thinning, hypertrabeculation, non-compaction, defective ventricular septation and left ventricular dilation (PubMed:21091282, PubMed:21068380, PubMed:23130124, PubMed:30389594). RNAi-mediated knockdown also results in impaired CL metabolism in the brain with reduced total CL levels and significantly increased MLCL levels, impaired brain mitochondrial respiration, elevated brain production of reactive oxygen species, significant memory deficiency, derangement of the hippocampal CA1 neuronal layer and elevated microglia activity (PubMed:30055293). Hepatic CL levels remain normal (PubMed:30055293). RNAi-mediated knockdown does not affect resting metabolic rate but markedly impairs oxygen consumption rates during exercise and diminishes mitochondrial complex III activity (PubMed:23616771). {ECO:0000269|PubMed:21068380, ECO:0000269|PubMed:21091282, ECO:0000269|PubMed:23130124, ECO:0000269|PubMed:23616771, ECO:0000269|PubMed:26114544, ECO:0000269|PubMed:30055293, ECO:0000269|PubMed:30389594}. |