Several neurodegenerative diseases are associated with defects in the gene ACOX1, which encodes peroxisomal acyl-CoA oxidase. This enzyme catalyzes the first and rate-limiting enzyme in the peroxisomal fatty acid beta-oxidation pathway. Both loss- and gain-of-function variants of ACOX1 lead to glial and neuronal loss, but by different mechanisms. See links in 'Related Diseases' for information on specific diseases associated with ACOX1.
The highest-scoring ortholog in Drosophila is also designated ACOX1; loss-of-function mutations, a gain-of-function allele analogous to human N237S, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\ACOX1.
Multiple UAS constructs of the human Hsap\ACOX1 have been introduced into flies, including wild-type and the N237S variant implicated in Mitchell syndrome (see FBhh0001229).
Animals homozygous for loss-of-function alleles of Dmel\ACOX1 typically die during the pupal stage; adult escapers exhibit progressive locomotor impairment and progressive vision defects leading to vision loss; TEM analysis of peripheral neurons in the wing showed decreased numbers of axons and wrapping glia. A small number of physical and genetic interactions of Dmel\ACOX1 have been described; see below and in the ACOX1 gene report.
[updated Jul. 2020 by FlyBase; FBrf0222196]
Peroxisomal beta-oxidation of fatty acids is catalyzed by enzymes that are immunologically distinct from the analogous mitochondrial enzymes. The ACOX1 gene encodes peroxisomal acyl-CoA oxidase, the first and rate-limiting enzyme in the peroxisomal fatty acid beta-oxidation pathway. [from MIM:609751; 2020.07.27]
Many to many: multiple related genes in both species.
High-scoring ortholog of human ACOX1; additional related genes in both species. Dmel\ ACOX1 shares 44% identity and 63% similarity with human ACOX1.
