Clinical Research Center, Department of Internal Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Department of Pathobiology and Laboratory Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Mitochondrion. 2021 Nov;61:85-101. doi: 10.1016/j.mito.2021.09.012. Epub 2021 Sep 30.
Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis.
线粒体是普遍存在的膜结合细胞器，不仅在维持细胞能量稳态和代谢方面发挥关键作用，而且在信号转导和细胞凋亡中也发挥重要作用。芳烃受体（AhR）是配体激活的转录因子，可识别多种外源物，包括多环芳烃和二恶英，并激活多种解毒途径。这些受体也被天然膳食化合物和内源性代谢物激活。此外，AhR 可以调节与线粒体生物发生和功能相关的多种基因的表达。本综述的目的是分析现有的关于 AhR 信号通路及其与涉及线粒体功能的细胞内信号通路相互作用的科学数据，特别是与细胞周期进程和细胞凋亡相关的信号通路。有各种证据表明 AhR 信号通路与核因子 κB（NF-κB）、酪氨酸激酶受体信号和丝裂原活化蛋白激酶（MAPKs）之间存在串扰。AhR 信号通路似乎在没有外源配体的情况下促进细胞周期进程，而外源配体的存在则诱导细胞周期停滞。然而，其对细胞凋亡的影响存在争议，因为 AhR 的激活或过表达被观察到诱导或抑制细胞凋亡，具体取决于细胞类型。关于线粒体，尽管内源性配体的激活与线粒体功能障碍有关，但内源性配体的作用尚不清楚，但指向抗细胞凋亡作用和诱导线粒体生物发生。
