Abstract |
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.
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Authors | Daniele Ghezzi, Paola Arzuffi, Mauro Zordan, Caterina Da Re, Costanza Lamperti, Clara Benna, Pio D'Adamo, Daria Diodato, Rodolfo Costa, Caterina Mariotti, Graziella Uziel, Cristina Smiderle, Massimo Zeviani |
Journal | Nature genetics
(Nat Genet)
Vol. 43
Issue 3
Pg. 259-63
(Mar 2011)
ISSN: 1546-1718 [Electronic] United States |
PMID | 21278747
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Codon, Nonsense
- Membrane Proteins
- Mitochondrial Proteins
- TTC19 protein, human
- Electron Transport Complex III
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Topics |
- Adult
- Animals
- Brain
(pathology)
- Codon, Nonsense
- Drosophila melanogaster
(genetics)
- Electron Transport Complex III
(deficiency, genetics)
- Female
- Gene Knockdown Techniques
- Humans
- Male
- Membrane Proteins
(genetics)
- Mitochondria
(genetics, metabolism)
- Mitochondrial Proteins
(genetics)
- Nervous System Diseases
(genetics, pathology)
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