Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies

作者：Ghezzi Daniele; Arzuffi Paola; Zordan Mauro; Da Re Caterina; Lamperti Costanza; Benna Clara; D'Adamo Pio; Diodato Daria; Costa Rodolfo; Mariotti Caterina; Uziel Graziella; Smiderle Cristina; Zeviani Massimo^*

来源：Nature Genetics, 2011, 43(3): 259-U109.

DOI：10.1038/ng.761

Although mutations in CYTB (cytochrome b) or BCS1L have been reported in isolated defects of mitochondrial respiratory chain complex III (cIII), most cIII-defective individuals remain genetically undefined. We identified a homozygous nonsense mutation in the gene encoding tetratricopeptide 19 (TTC19) in individuals from two families affected by progressive encephalopathy associated with profound cIII deficiency and accumulation of cIII-specific assembly intermediates. We later found a second homozygous nonsense mutation in a fourth affected individual. We demonstrated that TTC19 is embedded in the inner mitochondrial membrane as part of two high-molecular-weight complexes, one of which coincides with cIII. We then showed a physical interaction between TTC19 and cIII by coimmunoprecipitation. We also investigated a Drosophila melanogaster knockout model for TTC19 that showed low fertility, adult-onset locomotor impairment and bang sensitivity, associated with cIII deficiency. TTC19 is a putative cIII assembly factor whose disruption is associated with severe neurological abnormalities in humans and flies.

• 出版日期2011-3