Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in
maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups
between acetyl-CoA and carnitine. Show more
Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in
maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups
between acetyl-CoA and carnitine. This enzymatic activity ensures the optimal functioning
of mitochondrial carbon flux by preventing acetyl-CoA accumulation, buffering metabolic
flexibility, and regulating the balance between fatty acid and glucose oxidation. CRAT’s interplay with the mitochondrial carnitine shuttle, involving carnitine palmitoyltransferases
(CPT1 and CPT2) and the carnitine carrier (SLC25A20), underscores its critical role in
energy metabolism. Emerging evidence highlights the structural and functional diversity of
CRAT and structurally related acetyltransferases across cellular compartments, illustrating
their coordinated role in lipid metabolism, amino acid catabolism, and mitochondrial
bioenergetics. Moreover, the structural insights into CRAT have paved the way for understanding its regulation and identifying potential modulators with therapeutic applications
for diseases such as diabetes, mitochondrial disorders, and cancer. This review examines
CRAT’s structural and functional aspects, its relationships with carnitine shuttle members
and other carnitine acyltransferases, and its broader role in metabolic health and disease.
The potential for targeting CRAT and its associated pathways offers promising avenues
for therapeutic interventions aimed at restoring metabolic equilibrium and addressing
metabolic dysfunction in disease states.
Luca, D.I.; Guerra, L.; Pierri, C.L.; De
Grassi, A. Carnitine
O-Acetyltransferase as a Central
Player in Lipid and Branched-Chain
Amino Acid Metabolism, Epigenetics, Show less
Cell lines are invaluable biomedical research tools, and recent literature has emphasized the importance of genotype authentication and characterization. In the present study, 24 out of 27 cell line i Show more
Cell lines are invaluable biomedical research tools, and recent literature has emphasized the importance of genotype authentication and characterization. In the present study, 24 out of 27 cell line identities were confirmed by short tandem repeat profiling. The molecular phenotypes of the 24 colon cancer cell lines were examined, and microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) were determined, using the Bethesda panel mononucleotide repeat loci and two epimarker panels, respectively. Furthermore, the BRAF, KRAS and PIK3CA oncogenes were analyzed for mutations in known hotspots, while the entire coding sequences of the PTEN and TP53 tumor suppressors were investigated. Nine cell lines showed MSI. Thirteen and nine cell lines were found to be CIMP positive, using the Issa panel and the Weisenberger et al. panel, respectively. The latter was found to be superior for CIMP classification of colon cancer cell lines. Seventeen cell lines harbored disrupting TP53 mutations. Altogether, 20/24 cell lines had the mitogen-activated protein kinase pathway activating mutually exclusive KRAS or BRAF mutations. PIK3CA and PTEN mutations leading to hyperactivation of the phosphoinositide 3-kinase/AKT pathway were observed in 13/24 cell lines. Interestingly, in four cell lines there were no mutations in neither BRAF, KRAS, PIK3CA nor in PTEN. In conclusion, this study presents molecular features of a large number of colon cancer cell lines to aid the selection of suitable in vitro models for descriptive and functional research. Show less