Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Sci Rep. 2021 Nov 2;11(1):21477. doi: 10.1038/s41598-021-00801-w.
Interactions between the endoplasmic reticulum (ER) and mitochondria (Mito) are crucial for many cellular functions, and their interaction levels change dynamically depending on the cellular environment. Little is known about how the interactions between these organelles are regulated within the cell. Here we screened a compound library to identify chemical modulators for ER-Mito contacts in HEK293T cells. Multiple agonists of G-protein coupled receptors (GPCRs), beta-adrenergic receptors (β-ARs) in particular, scored in this screen. Analyses in multiple orthogonal assays validated that β2-AR activation promotes physical and functional interactions between the two organelles. Furthermore, we have elucidated potential downstream effectors mediating β2-AR-induced ER-Mito contacts. Together our study identifies β2-AR signaling as an important regulatory pathway for ER-Mito coupling and highlights the role of these contacts in responding to physiological demands or stresses.
内质网 (ER) 和线粒体 (Mito) 之间的相互作用对于许多细胞功能至关重要，它们的相互作用水平会根据细胞环境动态变化。目前对于这些细胞器在细胞内的相互作用是如何被调控的知之甚少。在这里，我们筛选了一个化合物库，以鉴定 HEK293T 细胞中 ER-Mito 接触的化学调节剂。该筛选中鉴定出了多种 G 蛋白偶联受体 (GPCR) 的激动剂，特别是β肾上腺素能受体 (β-AR)。在多种正交测定中分析验证了β2-AR 的激活促进了这两个细胞器之间的物理和功能相互作用。此外，我们已经阐明了潜在的下游效应物介导β2-AR 诱导的 ER-Mito 接触。我们的研究共同确定了β2-AR 信号作为 ER-Mito 偶联的重要调节途径，并强调了这些接触在响应生理需求或应激中的作用。
