
-   p53 induces CROT transcription through binding to consensus response elements in the 5'-UTR of CROT mRNA following nutrient starvation [PMID: 37307919].
-   Enzyme activity measurements showed that COT efficiently converts one of the end products of the peroxisomal beta-oxidation of pristanic acid, 4, 8-dimethylnonanoyl-CoA, to its corresponding carnitine ester. Production of the carnitine ester of this branched/medium-chain acyl-CoA within the peroxisome is required for its transport to the mitochondrion where further beta-oxidation occurs [PMID: 10486279].
-   CROT is a peroxisomal enzyme involved in fatty acid metabolism. In hepatic cells, alteration in CROT expression induced changes in lipid profile. An increase in CROT activity induced a decrease in MCFA and very long chain fatty acids (VLCFA) levels. CROT activity, by controlling the peroxisomal amount of medium chain acyls, may control the peroxisomal oxidative pathway [PMID: 21619872].

## Summary

CROT, encoded by the Crot gene, plays a crucial role in lipid metabolism and fatty acid beta-oxidation in the liver [CS: 9]. In cases of liver disease or toxicity, the dysregulation of CROT can be mechanistically understood through its involvement in these processes [CS: 8]. For instance, under conditions of nutrient starvation, p53, a protein involved in cellular stress responses, upregulates CROT transcription [CS: 7]. This upregulation aids in the efficient utilization of stored very long-chain fatty acids, promoting oxidative metabolism and cell survival [CS: 8]. In this context, CROT's increased activity helps the liver adapt to nutrient scarcity by enhancing the breakdown of stored fats into energy, a critical survival mechanism during periods of limited nutrient availability [CS: 9].

Conversely, in conditions like hepatocarcinogenesis, CROT is downregulated in human hepatoma cells overexpressing the androgen receptor (AR) [CS: 5]. This reduction in CROT levels may contribute to altered fatty acid metabolism, as CROT is integral to the conversion of acyl-CoA molecules to their carnitine esters, facilitating their transport out of peroxisomes [CS: 9]. Such impairment in fatty acid metabolism could exacerbate liver dysfunction in cancerous conditions [CS: 8]. Additionally, the dysregulation of CROT in liver diseases and toxicities reflects its role in maintaining lipid homeostasis [CS: 9]. In hepatic cells, alterations in CROT expression impact levels of medium chain fatty acids (MCFA) and very long-chain fatty acids (VLCFA), indicating its critical function in controlling peroxisomal oxidative pathways and overall lipid balance in the liver [CS: 9].
