Literature summary for 1.14.13.9 extracted from

Maddison, D.C.; Alfonso-Nunez, M.; Swaih, A.M.; Breda, C.; Campesan, S.; Allcock, N.; Straatman-Iwanowska, A.; Kyriacou, C.P.; Giorgini, F.
A novel role for kynurenine 3-monooxygenase in mitochondrial dynamics (2020), PLoS Genet., 16, e1009129 .

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Cloned(Commentary)

Cloned (Comment)	Organism
gene cinnabar, quantitative enzyme expression analysis, gene cinnabar genetically interacts with the Parkinson's disease associated genes Pink1 and parkin, as well as the mitochondrial fission gene Drp1, implicating KMO in mitochondrial dynamics and mitophagy, mechanisms which govern the maintenance of a healthy mitochondrial network. Overexpression of human KMO in HEK-293T cells. Cinnabar genetically interacts with Pink1 and parkin in a mechanism independent of KP metabolism, overview	Drosophila melanogaster

Cloned (Comment)

Organism

gene cinnabar, quantitative enzyme expression analysis, gene cinnabar genetically interacts with the Parkinson's disease associated genes Pink1 and parkin, as well as the mitochondrial fission gene Drp1, implicating KMO in mitochondrial dynamics and mitophagy, mechanisms which govern the maintenance of a healthy mitochondrial network. Overexpression of human KMO in HEK-293T cells. Cinnabar genetically interacts with Pink1 and parkin in a mechanism independent of KP metabolism, overview

Drosophila melanogaster

Protein Variants

Protein Variants	Comment	Organism
additional information	cinnabar null cn3 line analysis, the aspect ratio and Feret's diameter are increased in cn3 flies compared to Canton S control flies, reflecting mitochondrial elongation arising from KMO deficiency. Mitochondrial respiratory capacity and locomotor activity are decreased in cn flies, independent from 3-hydroxy-L-kynurenine (3-HK) synthesis. Gene cinnabar silencing with about 80% knockdown resulting in an elongation of the mitochondrial network compared with cells treated with the control dsRNAi construct, phenotype overview. Drp1 upregulation reverses climbing phenotype of cn-deficient flies	Drosophila melanogaster

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrial outer membrane	KMO is localized to the outer mitochondrial membrane in eukaryotic organisms	Drosophila melanogaster	5741	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-kynurenine + NADPH + H+ + O2	Drosophila melanogaster	-	3-hydroxy-L-kynurenine + NADP+ + H2O	-	?
L-kynurenine + NADPH + H+ + O2	Drosophila melanogaster Canton S	-	3-hydroxy-L-kynurenine + NADP+ + H2O	-	?

Organism

Organism	UniProt	Comment	Textmining
Drosophila melanogaster	A1Z746	-	-
Drosophila melanogaster Canton S	A1Z746	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
eye	cinnabar expression is highly enriched in the Drosophila compound eye	Drosophila melanogaster	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-kynurenine + NADPH + H+ + O2	-	Drosophila melanogaster	3-hydroxy-L-kynurenine + NADP+ + H2O	-	?
L-kynurenine + NADPH + H+ + O2	-	Drosophila melanogaster Canton S	3-hydroxy-L-kynurenine + NADP+ + H2O	-	?

Synonyms

Synonyms	Comment	Organism
cinnabar	-	Drosophila melanogaster
KMO	-	Drosophila melanogaster

Cofactor

Cofactor	Comment	Organism	Structure
FAD	-	Drosophila melanogaster
NADPH	-	Drosophila melanogaster

General Information

General Information	Comment	Organism
malfunction	KMO-deficient Drosophila melanogaster shows mitochondrial phenotypes in vitro and in vivo, overview. Loss of function allele or RNAi knockdown of the Drosophila KMO orthologue gene cinnabar causes a range of morphological and functional alterations to mitochondria, which are independent of changes to levels of KP metabolites. Elongated mitochondria are observed in cinnabar deficient fly models. Mitochondrial DRP1 Ser637 phosphorylation is reduced by KMO overexpression, resulting in an increase in mitochondrial fission	Drosophila melanogaster
metabolism	enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. KMO modulates DRP1 post-translational regulation	Drosophila melanogaster
physiological function	role for kynurenine 3-monooxygenase in mitochondrial dynamics. KMO plays a role in the post-translational regulation of DRP1, mitochondrial role for KMO, independent from its enzymatic role in the kynurenine pathway (KP)	Drosophila melanogaster