TWINKLE and Other Human Mitochondrial DNA Helicases: Structure, Function and Disease

Genes (Basel). 2020 Apr 9;11(4):408. doi: 10.3390/genes11040408.


Mammalian mitochondria contain a circular genome (mtDNA) which encodes subunits of the oxidative phosphorylation machinery. The replication and maintenance of mtDNA is carried out by a set of nuclear-encoded factors-of which, helicases form an important group. The TWINKLE helicase is the main helicase in mitochondria and is the only helicase required for mtDNA replication. Mutations in TWINKLE cause a number of human disorders associated with mitochondrial dysfunction, neurodegeneration and premature ageing. In addition, a number of other helicases with a putative role in mitochondria have been identified. In this review, we discuss our current knowledge of TWINKLE structure and function and its role in diseases of mtDNA maintenance. We also briefly discuss other potential mitochondrial helicases and postulate on their role(s) in mitochondria.

Keywords: PEO; TWINKLE; mitochondria; mtDNA; replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism*
  • DNA Replication
  • DNA, Mitochondrial / metabolism
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / physiology*
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / physiopathology*
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / metabolism*
  • Mutation
  • Oxidative Phosphorylation


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • DNA Helicases
  • TWNK protein, human