title: Regulation of brefeldin A-induced ER stress and apoptosis by mitochondrial NADP⁺-dependent isocitrate dehydrogenase.
abstract: 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.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
authors.forename: Jung Lee
authors.initials: JL
authors.lastname: Moon
authors.forename: Sung Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Seoung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020126:Brefeldin A / Q000494:pharmacology*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D020126:Brefeldin A; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)