title: Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency.
abstract: Human UBIAD1 localizes to mitochondria and converts vitamin K(1) to vitamin K(2). Vitamin K(2) is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K(2) exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson's disease that affects mitochondrial function. We found that vitamin K(2) was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K(2), and, similar to ubiquinone, vitamin K(2) transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Vos
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Janaka N
authors.initials: JN
authors.lastname: Edirisinghe
authors.forename: Sven
authors.initials: S
authors.lastname: Vilain
authors.forename: Dominik M
authors.initials: DM
authors.lastname: Haddad
authors.forename: Jan R
authors.initials: JR
authors.lastname: Slabbaert
authors.forename: Stefanie
authors.initials: S
authors.lastname: Van Meensel
authors.forename: Onno
authors.initials: O
authors.lastname: Schaap
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
authors.forename: R
authors.initials: R
authors.lastname: Meganathan
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Morais
authors.forename: Patrik
authors.initials: P
authors.lastname: Verstreken
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D004579:Electron Transport; D004926:Escherichia coli / Q000378:metabolism; D005426:Flight, Animal; D017344:Genes, Insect; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation; D010101:Oxygen Consumption; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D024482:Vitamin K 2 / Q000378:metabolism* / Q000494:pharmacology; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000255:Adenosine Triphosphate; D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D014451:Ubiquinone; D044767:Ubiquitin-Protein Ligases; D024482:Vitamin K 2; C572967:heix protein, Drosophila; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase; C487430:park protein, Drosophila