Regulation of brefeldin A-induced ER stress and apoptosis by mitochondrial NADP⁺-dependent isocitrate dehydrogenase.

Biochem Biophys Res Commun

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.

Published: January 2012

Brefeldin A (BFA), an endoplasmic reticulum (ER)-Golgi transport inhibitor, has been shown to cause accumulation of proteins in the ER, ER stress, and ultimately apoptosis. In this paper, we demonstrate that the knockdown of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm), a mitochondrial NADPH-generating enzyme, by small interfering RNA (siRNA) enhanced BFA-induced apoptosis. However, attenuated IDPm activity results in the suppression of ER stress response, presumably, via the inhibition of the PI3K/Akt pathway. Collectively, our data suggest that the association of IDPm expression and ER stress confers a survival mechanism in A549 cells against BFA-induced apoptosis.

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http://dx.doi.org/10.1016/j.bbrc.2011.12.030DOI Listing

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