Acot6, an acyl-CoA thioesterase, is specifically involved in the metabolism of phytanic acid and pristanic acid [1]. These acids are derived from phytol, with phytanic acid undergoing alpha-oxidation to pristanic acid in peroxisomes, where Acot6 acts as an auxiliary enzyme in both alpha-and beta-oxidation pathways of methyl-branched fatty acids. It is also associated with the biosynthesis of unsaturated fatty acids [2].

In mouse studies, sequence analysis of Acot6 revealed a peroxisomal targeting signal at the C-terminal end, and it was verified as a peroxisomal enzyme [1]. Subcellular fractionation experiments showed high phytanoyl-CoA/pristanoyl-CoA thioesterase activity in peroxisomes, which could be immunoprecipitated using an Acot6 antibody. Acot6 mRNA was mainly expressed in white adipose tissue and co-expressed with Acox3 in some tissues. It was identified as a target gene of PPARalpha and up-regulated in mouse liver in a PPARalpha-dependent manner [1]. In ducks, dietary linseed oil affected the expression of Acot6 related to unsaturated fatty acid biosynthesis [2]. In clear cell renal cell carcinoma, Acot6 was among the genes associated with smoking-related ccRCC, though its exact role in this context from the study was not as clearly defined as its metabolic roles [3].

In conclusion, Acot6 is crucial for the metabolism of specific fatty acids, playing a role in peroxisomal alpha-and beta-oxidation pathways. Its expression can be regulated by dietary factors and is associated with certain disease-related gene expression patterns. Mouse models have been valuable in revealing its function in fatty acid metabolism, while in disease-related research, it shows potential associations with smoking-related clear cell renal cell carcinoma, though further exploration is needed to clarify its role in this disease [1,2,3].