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首页> 外文期刊>Cell Health and Cytoskeleton >Role of apoptosis-inducing factor, proline dehydrogenase, and NADPH oxidase in apoptosis and oxidative stress
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Role of apoptosis-inducing factor, proline dehydrogenase, and NADPH oxidase in apoptosis and oxidative stress

机译：凋亡诱导因子，脯氨酸脱氢酶和NADPH氧化酶在细胞凋亡和氧化应激中的作用

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Abstract: Flavoproteins catalyze a variety of reactions utilizing flavin mononucleotide or flavin adenine dinucleotide as cofactors. The oxidoreductase properties of flavoenzymes implicate them in redox homeostasis, oxidative stress, and various cellular processes, including programmed cell death. Here we explore three critical flavoproteins involved in apoptosis and redox signaling, ie, apoptosis-inducing factor (AIF), proline dehydrogenase, and NADPH oxidase. These proteins have diverse biochemical functions and influence apoptotic signaling by unique mechanisms. The role of AIF in apoptotic signaling is two-fold, with AIF changing intracellular location from the inner mitochondrial membrane space to the nucleus upon exposure of cells to apoptotic stimuli. In the mitochondria, AIF enhances mitochondrial bioenergetics and complex I activity/assembly to help maintain proper cellular redox homeostasis. After translocating to the nucleus, AIF forms a chromatin degrading complex with other proteins, such as cyclophilin A. AIF translocation from the mitochondria to the nucleus is triggered by oxidative stress, implicating AIF as a mitochondrial redox sensor. Proline dehydrogenase is a membrane-associated flavoenzyme in the mitochondrion that catalyzes the rate-limiting step of proline oxidation. Upregulation of proline dehydrogenase by the tumor suppressor, p53, leads to enhanced mitochondrial reactive oxygen species that induce the intrinsic apoptotic pathway. NADPH oxidases are a group of enzymes that generate reactive oxygen species for oxidative stress and signaling purposes. Upon activation, NADPH oxidase 2 generates a burst of superoxide in neutrophils that leads to killing of microbes during phagocytosis. NADPH oxidases also participate in redox signaling that involves hydrogen peroxide-mediated activation of different pathways regulating cell proliferation and cell death. Potential therapeutic strategies for each enzyme are also highlighted.
机译：摘要：黄素蛋白以黄素单核苷酸或黄素腺嘌呤二核苷酸为辅因子催化多种反应。黄酮酶的氧化还原酶特性使它们参与氧化还原稳态，氧化应激和各种细胞过程，包括程序性细胞死亡。在这里，我们探讨了参与凋亡和氧化还原信号转导的三个关键黄素蛋白，即凋亡诱导因子（AIF），脯氨酸脱氢酶和NADPH氧化酶。这些蛋白质具有多种生化功能，并通过独特的机制影响凋亡信号转导。 AIF在凋亡信号传导中的作用是双重的，当细胞暴露于凋亡刺激时，AIF会改变细胞内位置，从线粒体内膜空间到细胞核。在线粒体中，AIF增强了线粒体的生物能，并增强了复合物I的活性/组装，以帮助维持适当的细胞氧化还原稳态。转移到细胞核后，AIF与其他​​蛋白（例如亲环蛋白A）形成染色质降解复合物。氧化应激触发AIF从线粒体到细胞核的转移，暗示AIF可能是线粒体氧化还原传感器。脯氨酸脱氢酶是线粒体中与膜相关的黄素酶，催化脯氨酸氧化的限速步骤。肿瘤抑制因子p53对脯氨酸脱氢酶的上调导致线粒体活性氧的增加，从而诱导内在的凋亡途径。 NADPH氧化酶是一组为氧化应激和信号传导目的而产生活性氧的酶。激活后，NADPH氧化酶2在嗜中性粒细胞中产生一阵超氧化物，导致吞噬过程中微生物的杀死。 NADPH氧化酶还参与氧化还原信号传导，该信号涉及过氧化氢介导的调节细胞增殖和细胞死亡的不同途径的激活。还强调了每种酶的潜在治疗策略。

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