Fig. 9. Schematic diagram of the role of CAND1 in regulating ubiquitination and degradation of ACAA2 and NAFLD.

Under normal condition, AR regulates the transcription of CAND1 by binding to its promoter region. CAND1 finetunes the ubiquitination and degradation of ACAA2 via the Cullin1/Fbxo42/ACAA2 complex to maintain fatty acid metabolism homeostasis. In NAFLD, decreased AR expression reduced CAND1 transcription. Reduction of CAND1 promotes the assembly of Cullin1, FBXO42, and ACAA2 complexes, and accelerates ubiquitinated degradation of ACAA2. which causes the insufficient β-oxidative capacity of fatty acids, accumulation of fatty acids, increased lipotoxicity in hepatocytes, and eventually NAFLD. The diagram was created using BioRender.