ER-phagy is an evolutionarily conserved mechanism crucial for maintaining cellular homeostasis. However, significant gaps persist in our understanding of how ER-phagy and the ER network vary across cell subtypes, tissues, and organs. Furthermore, the pathophysiological relevance of ER-phagy remains poorly elucidated. Addressing these questions requires developing quantifiable methods to visualize ER-phagy and ER architecture in vivo. We generated two transgenic mouse lines expressing an ER lumen-targeting tandem RFP-GFP (ER-TRG) tag, either constitutively or conditionally. This approach enables precise spatiotemporal measurements of ER-phagy and ER structure at single-cell resolution in vivo. Systemic analysis across diverse organs, tissues, and primary cultures derived from these ER-phagy reporter mice unveiled significant variations in basal ER-phagy, both in vivo and ex vivo. Furthermore, our investigation uncovered substantial remodeling of ER-phagy and the ER network in different tissues under stressed conditions such as starvation, oncogenic transformation, and tissue injury. In summary, both reporter models represent valuable resources with broad applications in fundamental research and translational studies.

中文翻译：

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在体内可视化 ER 自噬和 ER 结构。


内质网自噬是一种进化上保守的机制，对维持细胞稳态至关重要。然而，我们对 ER 自噬和 ER 网络如何因细胞亚型、组织和器官而异的理解仍然存在重大差距。此外，ER 自噬的病理生理相关性仍然难以阐明。解决这些问题需要开发可量化的方法，以可视化体内 ER 自噬和 ER 结构。我们生成了两个组成型或条件性表达 ER 腔靶向串联 RFP-GFP （ER-TRG） 标签的转基因小鼠系。这种方法能够在体内以单细胞分辨率对 ER 噬态和 ER 结构进行精确的时空测量。对源自这些 ER 自噬报告小鼠的不同器官、组织和原代培养物的系统分析揭示了体内和体外基础 ER 自噬的显着变化。此外，我们的调查发现，在饥饿、致癌转化和组织损伤等应激条件下，不同组织中 ER 噬和 ER 网络的大量重塑。总之，这两种报告基因模型都代表了宝贵的资源，在基础研究和转化研究中具有广泛的应用。