Richman 2016 Nat Commun
|Richman TR, Spåhr H, Ermer JA, Davies SM, Viola HM, Bates KA, Papadimitriou J, Hool LC, Rodger J, Larsson NG, Rackham O, Filipovska A (2016) Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice. Nat Commun 7:11884.|
Abstract: The recognition and translation of mammalian mitochondrial mRNAs are poorly understood. To gain further insights into these processes in vivo, we characterized mice with a missense mutation that causes loss of the translational activator of cytochrome oxidase subunit I (TACO1). We report that TACO1 is not required for embryonic survival, although the mutant mice have substantially reduced COXI protein, causing an isolated complex IV deficiency. We show that TACO1 specifically binds the mt-Co1 mRNA and is required for translation of COXI through its association with the mitochondrial ribosome. We determined the atomic structure of TACO1, revealing three domains in the shape of a hook with a tunnel between domains 1 and 3. Mutations in the positively charged domain 1 reduce RNA binding by TACO1. The Taco1 mutant mice develop a late-onset visual impairment, motor dysfunction and cardiac hypertrophy and thus provide a useful model for future treatment trials for mitochondrial disease.
Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine
Stress:Mitochondrial disease Organism: Mouse Tissue;cell: Heart, Liver Preparation: Isolated mitochondria Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase
Coupling state: LEAK, OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k