Arruda Ana Paula, Parlakgül Güneş
Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, California 94720, USA.
Chan Zuckerberg Biohub, San Francisco, California 94158, USA.
Cold Spring Harb Perspect Biol. 2023 Feb 1;15(2):a041261. doi: 10.1101/cshperspect.a041261.
The endoplasmic reticulum (ER) is a key organelle involved in the regulation of lipid and glucose metabolism, proteostasis, Ca signaling, and detoxification. The structural organization of the ER is very dynamic and complex, with distinct subdomains such as the nuclear envelope and the peripheral ER organized into ER sheets and tubules. ER also forms physical contact sites with all other cellular organelles and with the plasma membrane. Both form and function of the ER are highly adaptive, with a potent capacity to respond to transient changes in environmental cues such as nutritional fluctuations. However, under obesity-induced chronic stress, the ER fails to adapt, leading to ER dysfunction and the development of metabolic pathologies such as insulin resistance and fatty liver disease. Here, we discuss how the remodeling of ER structure and contact sites with other organelles results in diversification of metabolic function and how perturbations to this structural flexibility by chronic overnutrition contribute to ER dysfunction and metabolic pathologies in obesity.
内质网（ER）是一个关键细胞器，参与脂质和葡萄糖代谢、蛋白质稳态、钙信号传导及解毒过程的调节。内质网的结构组织非常动态且复杂，具有不同的亚结构域，如核膜和外周内质网，它们组织形成内质网片层和小管。内质网还与所有其他细胞器以及质膜形成物理接触位点。内质网的形态和功能都具有高度适应性，具有对营养波动等环境线索的短暂变化做出反应的强大能力。然而，在肥胖诱导的慢性应激下，内质网无法适应，导致内质网功能障碍以及胰岛素抵抗和脂肪肝疾病等代谢性疾病的发生。在此，我们讨论内质网结构及其与其他细胞器接触位点的重塑如何导致代谢功能的多样化，以及慢性营养过剩对这种结构灵活性的干扰如何导致肥胖中的内质网功能障碍和代谢性疾病。
