Twinkle mitochondrial DNA helicase (TWNK)

Twinkle mitochondrial DNA helicase (TWNK) is a crucial hexameric enzyme localized to mitochondria, functioning as the primary helicase responsible for unwinding mitochondrial DNA (mtDNA) to enable its replication and maintenance[1][2][3][4][5]. TWNK is part of the SF4 superfamily of helicases and exhibits 5′ to 3′ DNA unwinding activity, working as a ring-shaped oligomer in concert with mitochondrial DNA polymerase gamma and other replisome factors[2][4][5]. Mutations in the TWNK gene are associated with several mitochondrial diseases, most notably autosomal dominant Progressive External Ophthalmoplegia (PEO), mitochondrial DNA depletion syndrome type 7 (MTDPS7), and infantile-onset spinocerebellar ataxia (IOSCA), reflecting its essential role in mtDNA maintenance for cellular energy function[3][5]. TWNK’s structure and function are evolutionarily related to bacteriophage T7 gp4 primase-helicase but has lost primase activity in mammals, relying instead on mitochondrial RNA polymerase for replication priming[2][4]. Loss of function, deficiency, or pathogenic mutations in TWNK compromise mtDNA integrity, leading to tissue-specific or multisystemic disorders, and as such, it is considered a critical enzyme for mitochondrial health[1][2][3][5].

Other names

TwinklePEO1C10orf2Twinkle mtDNA helicaseT7 gp4-like protein with intramitochondrial nucleoid localizationT7-like mitochondrial DNA helicaseProgressive external ophthalmoplegia 1 proteinATXN8IOSCAMTDPS7PEOA3PRLTS5SANDOSCA8TwinkyFLJ21832TWINL

Not applicable (no direct drugs); disorders are caused by loss or mutation of TWNK leading to mtDNA depletion or deletions[3][5].