ABCB7 simultaneously regulates apoptotic and non-apoptotic cell death by modulating mitochondrial ROS and HIF1α-driven NFκB signaling.,Oncogene

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ABCB7 simultaneously regulates apoptotic and non-apoptotic cell death by modulating mitochondrial ROS and HIF1α-driven NFκB signaling.
Oncogene ( IF 6.9 ) Pub Date : 2019-11-26 , DOI: 10.1038/s41388-019-1118-6
Jung Yun Kim _{1,

2} , Jun-Kyum Kim _{1,

2} , Hyunggee Kim _{1,

2,

3}

Affiliation

Most of the mechanisms governing apoptotic and non-apoptotic cell death are regulated independently. However, cells may experience various stresses that lead to both apoptotic and non-apoptotic cell death. In particular, cancer cells require a program that simultaneously avoids these forms of cell death, but the mechanism by which they are able to do so is currently unclear. Here, we show that ABC transporter subfamily B member 7 (ABCB7), one of the mitochondrial iron transporters, induces the hypoxia-independent accumulation of hypoxia-inducible factor 1 alpha by controlling intracellular iron homeostasis and inhibits both apoptotic and non-apoptotic cell death. Mechanistically, ABCB7 mitigates non-apoptotic cell death by reducing levels of mitochondrial reactive oxygen species. ABCB7 also suppresses apoptosis by inhibiting the expression of leucine zipper downregulated in cancer 1, an inhibitor of nuclear factor-kappa B signaling. Therefore, our results support that ABCB7 is crucial in controlling both apoptotic and non-apoptotic cell death and indicate that the fine-tuning of intracellular iron homeostasis may be a novel anticancer strategy.

中文翻译：

ABCB7 通过调节线粒体 ROS 和 HIF1α 驱动的 NFκB 信号传导同时调节凋亡和非凋亡细胞死亡。

大多数控制凋亡和非凋亡细胞死亡的机制都是独立调节的。然而，细胞可能会经历导致凋亡和非凋亡细胞死亡的各种压力。特别是，癌细胞需要一个同时避免这些形式的细胞死亡的程序，但它们能够做到这一点的机制目前尚不清楚。在这里，我们展示了 ABC 转运蛋白亚家族 B 成员 7 (ABCB7)，线粒体铁转运蛋白之一，通过控制细胞内铁稳态诱导缺氧诱导因子 1 α 的缺氧非依赖性积累，并抑制凋亡和非凋亡细胞死亡. 从机制上讲，ABCB7 通过降低线粒体活性氧的水平来减轻非凋亡性细胞死亡。ABCB7 还通过抑制癌症 1 中下调的亮氨酸拉链的表达来抑制细胞凋亡，癌症 1 是一种核因子-kappa B 信号传导的抑制剂。因此，我们的结果支持 ABCB7 在控制凋亡和非凋亡细胞死亡方面至关重要，并表明细胞内铁稳态的微调可能是一种新的抗癌策略。

更新日期：2019-11-27

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