Bassot Arthur, Chen Junsheng, Simmen Thomas
Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Contact (Thousand Oaks). 2021 Mar 24;4:25152564211001213. doi: 10.1177/25152564211001213. eCollection 2021 Jan-Dec.
Cells must adjust their redox state to an ever-changing environment that could otherwise result in compromised homeostasis. An obvious way to adapt to changing redox conditions depends on cysteine post-translational modifications (PTMs) to adapt conformation, localization, interactions and catalytic activation of proteins. Such PTMs should occur preferentially in the proximity of oxidative stress sources. A particular concentration of these sources is found near membranes where the endoplasmic reticulum (ER) and the mitochondria interact on domains called MERCs (Mitochondria-Endoplasmic Reticulum Contacts). Here, fine inter-organelle communication controls metabolic homeostasis. MERCs achieve this goal through fluxes of Ca ions and inter-organellar lipid exchange. Reactive oxygen species (ROS) that cause PTMs of mitochondria-associated membrane (MAM) proteins determine these intertwined MERC functions. Chronic changes of the pattern of these PTMs not only control physiological processes such as the circadian clock but could also lead to or worsen many human disorders such as cancer and neurodegenerative diseases.
细胞必须将其氧化还原状态调整至不断变化的环境中，否则可能导致体内平衡受损。适应氧化还原条件变化的一种明显方式取决于半胱氨酸的翻译后修饰（PTM），以适应蛋白质的构象、定位、相互作用和催化激活。此类PTM应优先发生在氧化应激源附近。在内质网（ER）和线粒体在称为MERC（线粒体 - 内质网接触点）的区域相互作用的膜附近发现了这些源的特定浓度。在这里，精细的细胞器间通讯控制着代谢稳态。MERC通过钙离子通量和细胞器间脂质交换实现这一目标。导致线粒体相关膜（MAM）蛋白发生PTM的活性氧（ROS）决定了这些相互交织的MERC功能。这些PTM模式的长期变化不仅控制诸如生物钟等生理过程，还可能导致或加剧许多人类疾病，如癌症和神经退行性疾病。
