title: Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
abstract: The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenance and organization remain largely unknown. We report here a novel mitochondrial protein, Twinkle, with structural similarity to phage T7 gene 4 primase/helicase and other hexameric ring helicases. Twinkle colocalizes with mtDNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO), associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity.
authors: Institute of Medical Technology & Tampere University Hospital, Tampere, Finland. hans.spelbrink@uta.fi
authors: J N
authors: JN
authors: Spelbrink
authors: F Y
authors: FY
authors: Li
authors: V
authors: V
authors: Tiranti
authors: K
authors: K
authors: Nikali
authors: Q P
authors: QP
authors: Yuan
authors: M
authors: M
authors: Tariq
authors: S
authors: S
authors: Wanrooij
authors: N
authors: N
authors: Garrido
authors: G
authors: G
authors: Comi
authors: L
authors: L
authors: Morandi
authors: L
authors: L
authors: Santoro
authors: A
authors: A
authors: Toscano
authors: G M
authors: GM
authors: Fabrizi
authors: H
authors: H
authors: Somer
authors: R
authors: R
authors: Croxen
authors: D
authors: D
authors: Beeson
authors: J
authors: J
authors: Poulton
authors: A
authors: A
authors: Suomalainen
authors: H T
authors: HT
authors: Jacobs
authors: M
authors: M
authors: Zeviani
authors: C
authors: C
authors: Larsson
mesh_terms: D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D004265:DNA Helicases; D019915:DNA Primase / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000453:epidemiology / Q000235:genetics*; D010154:Pakistan / Q000453:epidemiology; D010375:Pedigree; D011487:Protein Conformation; D021381:Protein Transport; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D019915:DNA Primase; D004265:DNA Helicases; C431576:TWNK protein, human