A novel role for kynurenine 3-monooxygenase in mitochondrial dynamics

In this study, KMO deficientDrosophila melanogaster were investigated for mitochondrial phenotypesin vitro andin vivo. We find that a loss of function allele or RNAi knockdown of theDrosophila KMO ortholog (cinnabar) causes a range of morphological and functional alterations to mitochondria, which are independent of changes to levels of KP metabolites. Notably,cinnabar genetically interacts with the Parkinson ’s disease associated genesPink1 andparkin, as well as the mitochondrial fission geneDrp1, implicating KMO in mitochondrial dynamics and mitophagy, mechanisms which govern the maintenance of a healthy mitochondrial network. Overexpression of human KMO in mammalian cells finds that KMO plays a role in the post-translational regulation of DRP1. These findings reveal a novel mitochondrial role for KMO, independent from its enzymatic role in the kynurenine pathway.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research