Acox2, or Acyl-CoA oxidase 2, is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation [1,4,5]. It functions in pathways related to lipid metabolism and is crucial for maintaining hepatic metabolic homeostasis [1]. Gene knockout models have been valuable in studying its function.

In Acox2 knockout (-/-) mice, there is a spontaneous development of liver cancer with lymphocytic infiltrate [1]. Non-histone lysine crotonylation (Kcr) levels are downregulated in the livers of these mice, and the Kcr signals show a different subcellular distribution in tumor and normal liver cells [1]. Quantitative analysis of the global crotonylome reveals that many downregulated non-histone Kcr sites are in mitochondrial and peroxisomal enzymes [1]. Also, in a study on hepatocellular carcinoma (HCC), overexpression of Acox2 reduced the proliferation and metastasis of liver cancer in vitro and in vivo through the PPARα pathway [2]. In prostate cancer, overexpressing Acox2 in cell lines hindered cell viability, colony formation, migration, and invasion, and was associated with decreased cellular lipid content and elevated ROS content [3].

In conclusion, Acox2 plays essential roles in lipid metabolism, oxidative stress, and maintaining hepatic metabolic homeostasis. Studies using Acox2 knockout mouse models have revealed its significance in liver cancer and prostate cancer, highlighting its potential as a therapeutic target or prognostic marker in these disease areas.