From the Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108 and.
the Department of Chemistry, Mathematics and Physics, Clarion University of Pennsylvania, Clarion, Pennsylvania 16214.
J Biol Chem. 2018 Sep 21;293(38):14707-14722. doi: 10.1074/jbc.RA118.004022. Epub 2018 Aug 9.
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein occasionally involved in cell death that primarily regulates mitochondrial energy metabolism under normal cellular conditions. AIF catalyzes the oxidation of NADH , yet the significance of this redox activity in cells remains unclear. Here, we show that through its enzymatic activity AIF is a critical factor for oxidative stress-induced activation of the mitogen-activated protein kinases JNK1 (c-Jun N-terminal kinase), p38, and ERK (extracellular signal-regulated kinase). AIF-dependent JNK1 signaling culminates in the cadherin switch, and genetic reversal of this switch leads to apoptosis when AIF is suppressed. Notably, this widespread ability of AIF to promote JNK signaling can be uncoupled from its more limited role in respiratory chain stabilization. Thus, AIF is a transmitter of extra-mitochondrial signaling cues with important implications for human development and disease.
凋亡诱导因子（AIF）是一种线粒体黄素蛋白，偶尔参与细胞死亡，主要在正常细胞条件下调节线粒体能量代谢。AIF 催化 NADH 的氧化，但这种氧化还原活性在细胞中的意义尚不清楚。在这里，我们表明，通过其酶活性，AIF 是氧化应激诱导的丝裂原活化蛋白激酶 JNK1（c-Jun N 末端激酶）、p38 和 ERK（细胞外信号调节激酶）激活的关键因素。AIF 依赖性 JNK1 信号传导最终导致钙粘蛋白转换，当抑制 AIF 时，这种转换的遗传逆转导致细胞凋亡。值得注意的是，AIF 促进 JNK 信号传导的这种广泛能力可以与其在呼吸链稳定中的更有限作用脱耦。因此，AIF 是一种具有重要意义的线粒体外信号转导因子，对人类的发育和疾病有重要影响。
