Vitamin K ₂ Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency

TLDR

Human UBIAD1 localizes to mitochondria and converts vitamin K1 to K2, a molecule known as a blood‑coagulation cofactor but also a bacterial membrane electron carrier, yet its carrier role in eukaryotic mitochondria remains unestablished. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a Parkinson’s disease gene that affects mitochondrial function. Vitamin K2 was shown to be necessary and sufficient for electron transfer in Drosophila mitochondria, rescuing Heix mutant mitochondrial defects and restoring efficient ATP production, thereby demonstrating its role as a mitochondrial electron carrier that mitigates pink1‑associated dysfunction.

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.