Oncotarget

Research Papers:

p73 regulates basal and starvation-induced liver metabolism in vivo

Zhaoyue He _, Massimiliano Agostini, He Liu, Gerry Melino, Hans-Uwe Simon

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Oncotarget. 2015; 6:33178-33190. https://doi.org/10.18632/oncotarget.5090

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Abstract

Zhaoyue He1,*, Massimiliano Agostini2,3,*, He Liu1, Gerry Melino2,3, Hans-Uwe Simon1

1Institute of Pharmacology, University of Bern, Bern, Switzerland

2Medical Research Council, Toxicology Unit, Leicester, United Kingdom

3Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy

*These authors have contributed equally to this work

Correspondence to:

Hans-Uwe Simon, e-mail: hus@pki.unibe.ch

Keywords: p73, starvation, metabolism, liver, autophagy

Received: June 24, 2015     Accepted: August 26, 2015     Published: September 07, 2015

ABSTRACT

As a member of the p53 gene family, p73 regulates cell cycle arrest, apoptosis, neurogenesis, immunity and inflammation. Recently, p73 has been shown to transcriptionally regulate selective metabolic enzymes, such as cytochrome c oxidase subunit IV isoform 1, glucose 6-phosphate dehydrogenase and glutaminase-2, resulting in significant effects on metabolism, including hepatocellular lipid metabolism, glutathione homeostasis and the pentose phosphate pathway. In order to further investigate the metabolic effect of p73, here, we compared the global metabolic profile of livers from p73 knockout and wild-type mice under both control and starvation conditions. Our results show that the depletion of all p73 isoforms cause altered lysine metabolism and glycolysis, distinct patterns for glutathione synthesis and Krebs cycle, as well as an elevated pentose phosphate pathway and abnormal lipid accumulation. These results indicate that p73 regulates basal and starvation-induced fuel metabolism in the liver, a finding that is likely to be highly relevant for metabolism-associated disorders, such as diabetes and cancer.


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