Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation [1,4,5]. It plays a crucial role in maintaining hepatic metabolic homeostasis, and its function is also associated with lipid metabolism and oxidative stress pathways [1,3]. Gene knockout mouse models have been valuable in studying Acox2's function.

In Acox2 knockout (-/-) mice, non-histone lysine crotonylation (Kcr) levels were downregulated in the liver. Kcr signals were concentrated in the nucleus of tumor cells but mostly in the cytoplasm of adjacent normal liver cells. Quantitative analysis of the global crotonylome showed that many downregulated non-histone Kcr sites were in mitochondrial and peroxisomal enzymes. Site-directed mutagenesis and transcriptome analysis further revealed that Ehhadh K572cr might have site-specific regulatory roles leading to increased DNA damage in vitro, suggesting Acox2 is a regulator of Kcr in hepatic metabolic homeostasis [1]. Also, Acox2 overexpression in hepatocellular carcinoma cell lines reduced their proliferation and migration abilities in vitro and in a subcutaneous xenograft tumor model, indicating a tumor suppressor role, potentially through the PPARα pathway [2]. In prostate cancer, overexpressing Acox2 in cell lines hindered cell viability, colony formation, migration, and invasion, along with decreased cellular lipid content and elevated ROS levels [3].

In conclusion, Acox2 is essential for maintaining normal physiological functions in the liver, especially in regulating hepatic metabolic homeostasis, lipid metabolism, and oxidative stress. Studies using Acox2 knockout mouse models have provided insights into its role in liver cancer, prostate cancer, and other disease-related biological processes, highlighting its potential as a therapeutic target in these disease areas [1,2,3].