The adenine nucleotide translocase type 1 (ANT1): a new factor in mitochondrial disease.
Mitochondrial disorders of oxidative phosphorylation (OXPHOS) comprise a growing list of potentially lethal diseases caused by mutations in either mitochondrial (mtDNA) or nuclear DNA (nDNA). Two such conditions, autosomal dominant progressive external ophthalmoplegia (adPEO) and Senger's Syndrome, are associated with dysfunction of the heart and muscle-specific isoform of the adenine nucleotide translocase (ANT1), a nDNA gene product that facilitates transport of ATP and ADP across the inner mitochondrial membrane. AdPEO is a mtDNA deletion disorder broadly characterized by pathology involving the eyes, skeletal muscle, and central nervous system. In addition to ANT1, mutations in at least two other nuclear genes, twinkle and POLG, have been shown to cause mtDNA destabilization associated with adPEO. Senger's syndrome is an autosomal recessive condition characterized by congenital heart defects, abnormalities of skeletal muscle mitochondria, cataracts, and elevated circulatory levels of lactic acid. This syndrome is associated with severe depletion of ANT1, which may be the result of an as yet unidentified ANT1-specific transcriptional or translational processing error. ANT1 has also been associated with a third condition, autosomal dominant facioscapulohumeral muscular dystrophy (FSHD), an adult onset disorder characterized by variable muscle weakness in the face, feet, shoulders, and hips. FSHD patients possess specific DNA deletions on chromosome 4, which appear to cause derepression of several nearby genes, including ANT1. Early development of FSHD may involve mitochondrial dysfunction and increased oxidative stress, possibly associated with overexpression of ANT1.
Sharer
J Daniel
JD
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. dsharer@genetics.uab.edu
D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D017353:Gene Deletion; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D008954:Models, Biological; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics / Q000378:metabolism; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics / Q000378:metabolism
D033741:Adenine Nucleotide Translocator 1; D004272:DNA, Mitochondrial