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Retraction: Fructose sensitizes pancreatic beta cells to TNFα-induced necroptosis (doi: 10.1242/bio.014712)

N. Shulga,J. G. Pastorino

Published 2015 in Biology Open

ABSTRACT

ABSTRACT The past half-century has witnessed a dramatic increase in the incidence of obesity and diabetes (Jacobson, 2004; Krilanovich, 2004). Both of these occurrences have been accompanied by an increase in the consumption of fructose. Unlike glucose, the metabolism of fructose is not subject to negative feed-back inhibition and can impose stress on intracellular energy stores (Ishimoto et al., 2012; Lanaspa et al., 2014, 2012). In the present study we identify the ability of fructose to increase the sensitivity of pancreatic beta cells to TNFα induced cytotoxicity. Exposure of pancreatic beta cells to fructose induced fructokinase and glut-5 expression, two proteins critical for the metabolism of fructose. Importantly, the increased metabolism of fructose by beta cells was accompanied by an increase in the expression of mitoNEET. MitoNEET is a 2Fe-2S cluster binding protein localized to the outer mitochondrial membrane (Wiley et al., 2007a). The increased expression of mitoNEET mediated an enhanced sensitivity of the pancreatic beta cells to TNFα induced cytotoxicity that was prevented by suppression of mitoNEET expression or pharmacological inhibition of its ability to release its 2Fe-2S cluster.

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