Acad11, an acyl-CoA dehydrogenase, is involved in fatty acid metabolism. It enables the catabolism of 4-hydroxy fatty acids (4-HAs) by phosphorylating 4-hydroxyacyl-CoAs via its kinase domain and then converting them into 2-enoyl-CoAs, which are conventional fatty acid β-oxidation (FAO) intermediates. Acad11 is peroxisomal and is responsible for the catabolism of longer-chain 4-HAs, thus playing a crucial role in mammalian 4-HA lipid catabolism [1].

In mice lacking Acad11, 4-HAs accumulate in the plasma while 3-and 5-hydroxy acids remain unchanged. This indicates that Acad11 is essential for the normal catabolism of 4-HAs in vivo. Additionally, in oncogenic-Ras-expressing cells, Acad11, as a p53-inducible fatty acid metabolism-related gene, is required for efficient oxidative phosphorylation (OXPHOS) and cell survival upon glucose starvation, suggesting its importance in p53-mediated pro-survival functions [2].

In summary, Acad11 is a key enzyme in the catabolism of 4-HAs, and its deficiency in mouse models leads to the abnormal accumulation of 4-HAs. It also plays a role in p53-related cell survival under glucose-starved conditions. Understanding Acad11's functions provides insights into lipid metabolism and related disease mechanisms, such as potential metabolic disorders associated with abnormal 4-HA metabolism.

References:

1. Rashan, Edrees H, Bartlett, Abigail K, Khana, Daven B, Simcox, Judith A, Pagliarini, David J. 2024. ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.01.09.574893. https://pubmed.ncbi.nlm.nih.gov/38260250/

2. Jiang, Dadi, LaGory, Edward L, Kenzelmann Brož, Daniela, Giaccia, Amato J, Attardi, Laura D. 2015. Analysis of p53 transactivation domain mutants reveals Acad11 as a metabolic target important for p53 pro-survival function. In Cell reports, 10, 1096-109. doi:10.1016/j.celrep.2015.01.043. https://pubmed.ncbi.nlm.nih.gov/25704813/