enzyme deficiency leads to a significant decrease in fatty acid beta-oxidation and adenosine triphosphate generation, combined with a reduced mitochondrial membrane potential, resulting in cellular apoptosis
enzyme inactivation inhibits cell growth and ATP production and decreases tumorigenicity of ovarian cancer cells in severe combined immunodeficiency mice
the enzyme is crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mitochondrial fatty acid beta-oxidation disorders
CPT1C expression correlates inversely with mammalian target of rapamycin pathway activation, and contributes to rapamycin resistance in murine primary tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo
isoform CPT1C expression is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1Cdepletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKalpha
measurements of enzyme activity in mitochondria isolated from newborn, 24-h-old, fed or fasted, and 5-months-old pigs. Acetate rather than ketone bodies is the predominant radiolabeled product, and its production increases twofold with increasing fatty acid oxidation during the first 24-h suckling period. The rate of acetogenesis is directly proportional to isoform CPT I activity. The high activity of CPT I in 24-h-suckling piglets is not attributable to an increase in CPT I gene expression, but rather to a large decrease in the sensitivity of CPT I to malonyl-CoA inhibition, which offsets a developmental decrease in affinity of CPT I for palmitoyl-CoA. Acetate is the primary product of hepatic mitochondrial beta-oxidation in Sus scrofa and regulation during early development is mediated primarily via kinetic modulation of isoform CPT I.
fasting does not significantly change Vmax and free carnitine content in liver. Catalytic efficiency (Vmax/Km) and the ratio free carnitine/Km increases in fish fasted for 4 days. Both indicators decline when fish fast for 12 days
heterologous expression of a constitutively active CPT1A variant in brown adipocyte cells leads to increased fatty acid oxidation, lipolysis, UCP1 protein levels and mitochondrial activity. Enhanced fatty acid oxidation reduces the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers
silencing of CPT1C by siRNA leads to a significant decrease in DNA synthesis and weaker colony-forming capacities in PANC-1 and MDA-MB-231 cells. CPT1C-depleted PANC-1 and MDA-MB-231 cells arrest the cell cycle in G1 phase, changing this cell population from 30.0% to 58.0% and 50.3% to 56.0%, respectively. Silencing increases intracellular lipid content by 1.45fold. CPT1C knockdown cells accumulate intracellular ROS, compared with the negative control, by 2.8fold and causes rapid RH123 dequenching to 36.8%, which impairs the mitochondrial electrochemical gradient and permeability transition
silencing of CPT2 by siRNA leads to a decrease in DNA synthesis, decreases replicating DNA by 19.9% in MDA-MB-231 cells, and results in weaker colony-forming capacities. CPT1B-depleted PANC-1 and MDA-MB-231 cells arrest the cell cycle in G1 phase. Knockdown of CPT2 downregulates the mRNA levels of ERRbeta/gamma, GABPalpha, CREB and upregulates CISD1
treatment with Nepsilon-(carboxymethyl)-lysine-bovine serum albumin and CPT2 knockdown induce fibrosis-related gene expression and damage mitochondrial membrane potential, leading to renal fibrosis and diabetic nephropathy. CPT2 overexpression reverses Nepsilon-(carboxymethyl)-lysine-induced fibrosis-related gene expression
when fatty acid oxidation is reduced by genetic knockdown of CPT1, the proliferation rate of cancer cells decreases nearly 2fold and cannot be restored by acetate or octanoic acid supplementation. CPT1 knockdowns have altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 has been approximately 90% inhibited by etomoxir do not. Mitochondria isolated from CPT1 knockdowns show depleted concentrations of complex structural and signaling lipids. Expression of a catalytically dead CPT1 in CPT1 knockdowns does not restore mitochondrial coupling