Selected Peer-Reviewed Articles:
Naquet, P., Kerr, E. W., Vickers, S. D. , and Leonardi R. (2020) “Regulation of coenzyme A levels by degradation: the 'Ins and Outs'”. Prog. Lipid Res 78, 101028
Kerr, E. W., Shumar, S. A., and Leonardi, R. (2019) "Nudt8 is a novel CoA diphosphohydrolase that resides in the mitochondria". FEBS Lett. 593, 1133-1143
Shumar, S. A., Kerr, E. W., Fagone, P., Infante, A. M., and Leonardi, R. (2019) "Overexpression of Nudt7 decreases bile acid levels and peroxisomal fatty acid oxidation in the liver". J. Lipid Res. 60, 1005-1019
Shumar, S. A., Kerr, E. W., Geldenhuys, W. J., Montgomery, G. E., Fagone, P., Thirawatananond, P., Saavedra, H., Gabelli, S. B., and Leonardi, R. (2018) “Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform”. J. Biol. Chem. 293, 4134-4148
Corbin, D.R., Rehg, J.E., Shepherd D.L., Stoilov, P., Percifield, R.J., Horner, L., Frase, S., Zhang, Y.M., Rock, C.O., Hollander, J.M., Jackowski, S. and Leonardi, R. (2017) "Excess coenzyme A reduces skeletal muscle performance and strength in mice overexpressing human PANK2" Mol. Genet. Metab. 120, 350-362
Shumar, S. A., Fagone, P., Alfonso-Pecchio, A., Gray, J. T., Rehg, J. E., Jackowski, S. and Leonardi, R. (2015) "Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice", PLoS One. 2015 Jun 8;10(6):e0130013
Sharma, L. K., Leonardi, R., Lin, W., Boyd, V. A., Goktug, A., Shelat, A. A., Chen, T., Jackowski, S., and Rock, C. O. (2015) "A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinases", J. Med. Chem. 58, 1563-1568
Leonardi, R., Rock, C. O., and Jackowski, S., (2014) "Pank1 deletion in leptin-deficient mice reduces hyperglycaemia and hyperinsulinaemia and modifies global metabolism without affecting insulin resistance", Diabetologia 57, 1466-1475
Alfonso-Pecchio, A., Garcia, M., Leonardi, R., and Jackowski, S., (2012) "Compartmentalization of mammalian pantothenate kinases", PLoS One 7, e49509. PMCID: PMC3496714.
Garcia, M., Leonardi, R., Zhang Y.-M., Rehg, J. E., and Jackowski, S. (2012) "Deletion of pantothenate kinases 1 and 2 disturbs glucose and ketone metabolism", PLoS One 7, e40871. PMCID: PMC3398950.
Cherian, P. T, Yao, J., Leonardi, R., Maddox, M. M., Luna, V. A., Rock, C. O., and Lee, R. E. (2012) "Acyl-sulfamates target the essential glycerol-phosphate acyltransferase (PlsY) in Gram-positive bacteria", Bioorg. Med. Chem. 20, 4985-4994. PMCID: PMC3471809.
Leonardi, R., Subramanian, C., Jackowski, S., and Rock, C. O. (2012) "Cancer-associated isocitrate dehydrogenase mutations inactivate NADPH-dependent reductive carboxylation", J. Biol. Chem. 287, 14615-14620. PMCID: PMC3340216.
Zhang, K., Wang, S., Malhotra, J., Hassler, J. R., Back, S. H., Wang, G., Chang, L., Xu, W., Miao, H., Leonardi, R., Chen, Y. E., Jackowski, S., and Kaufman, R. J. (2011) "The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis", EMBO J. 30, 1357-1375. PMCID: PMC3094110.
Book Chapters, Reviews and Other Articles:
Jackowski, S., and Leonardi, R. (2014) "Deregulated coenzyme A, loss of metabolic flexibility and diabetes", Biochem. Soc. Trans. 42, 1118-1122
Leonardi, R., and Jackowski, S. (2013) "Coenzyme A: when small is mighty" ASBMB today 12, 56-57
Leonardi, R., and Jackowski, S. (2007) "Biosynthesis of Pantothenic acid and Coenzyme A, in: EcoSal-Escherichia coli and Salmonella: cellular and molecular biology". [Online] Module 18.104.22.168. http//www.ecosal.org. ASM Press, Washington, DC
Leonardi, R., Zhang, Y.-M., Rock, C. O., and Jackowski, S. (2005) "Coenzyme A: Back in action", Prog. Lipid Res. 44, 125-153
2014 - Oral communication winner, Coenzyme A and its Derivatives in Cellular metabolism and Disease, Biochemical Society Focused Meeting
Coenzyme A (CoA) is an essential and universally distributed cofactor that acts as the major acyl group carrier in the cell. Free CoA and acyl-CoAs are involved in hundreds of metabolic reactions, and are among a selected number of small molecules that have the ability to act as global regulators of cellular metabolism. Consistent with this key function, CoA levels are at the same time tightly regulated and flexible, so that the available supply is sufficiently adaptive to metabolic challenges such as fasting or a high fat diet. Regulation of CoA levels occurs through coordination of synthesis and degradation. In the liver, modulation of the amount of CoA contributes to the metabolic flexibility of this organ and to its ability to maintain glucose homeostasis during a fast. Conversely, in diabetic mice, hepatic CoA levels are abnormally high and unresponsive to changes in the nutritional state.
Not much is known about CoA degradation. The goal of our research is to establish the importance of two recently discovered CoA-degrading enzymes, Nudt7 and Nudt19, in the regulation of CoA levels and glucose homeostasis. In particular, we are interested in studying these enzymes in the context of diabetes and other metabolic diseases using a combination of biochemistry, animal studies and metabolomics.