Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene LF-like protein localized in mitochondria

The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenan ce and organization remain largely unknown. We report here a novel mitochon drial protein. Twinkle, with structural similarity to phage T7 gene 4 prima se/helicase and other hexameric ring helicases. Twinkle colocalizes with mt DNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in i ndividuals with autosomal dominant progressive external ophthalmoplegia (ad PEO). associated with multiple mtDNA deletions, identified 11 different cod ing-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations duster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle i s inferred to be critical for lifetime maintenance of human mtDNA integrity .