Abstract
The Tim23 protein is the key component of the mitochondrial import machinery. It locates to the inner mitochondrial membrane and its own import is dependent on the DDP1/TIM13 complex. Mutations in human DDP1 cause the Mohr-Tranebjaerg syndrome (MTS/DFN-1; OMIM #304700), which is one of the two known human diseases of the mitochondrial protein import machinery. We created a Tim23 knockout mouse from a gene trap embryonic stem cell clone. Homozygous Tim23 mice were not viable. Heterozygous F1 mutants showed a 50% reduction of Tim23 protein in Western blot, a neurological phenotype and a markedly reduced life span. Haploinsufficiency of the Tim23 mutation underlines the critical role of the mitochondrial import machinery for maintaining mitochondrial function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blastocyst / physiology
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Forelimb / physiology
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Genotype
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Hand Strength
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Humans
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Life Expectancy*
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Membrane Proteins / deficiency*
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Membrane Transport Proteins / genetics
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Mice
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Mice, Knockout
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Mitochondria / genetics*
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Precursor Protein Import Complex Proteins
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Mitochondrial Proteins / deficiency
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Mitochondrial Proteins / genetics
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Mutation*
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Orofaciodigital Syndromes / genetics
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Phenotype
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Protein Transport / genetics
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Rotarod Performance Test
Substances
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Membrane Proteins
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Membrane Transport Proteins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Precursor Protein Import Complex Proteins
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Mitochondrial Proteins
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TIMM8A protein, human
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Timm23 protein, mouse