JOURNAL OF CELL BIOLOGY
·
2024
·Vol. 223
·期 12
·e202408061
·
IF 7.4
Sang Yongjuan,Li Boran,Su Tinglin,Zhan Hanyu,Xiong Yue,Huang Zhiming,Wang Changjing,Cong Xiaoxia,Du Mengjie,Wu Yang,Yu Hang,Yang Xi,Ding Kezhi,Wang Xuhua,Miao Xiaolong,Gong Weihua,Wang Liang,Zhao Jingwei,Zhou Yiting,Liu Wei,Hu Xinyang,Sun Qiming
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.
研究领域:
细胞生物学
·
分子生物学
·
遗传学
✓ 已验证
DOI
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 18
·8796-8805
·
IF 7.233
Yimin Wang,Zhao Zhao,Fujing Wei,Zewei Luo,Yixiang Duan
Autophagic degradation of the endoplasmic reticulum (ER-phagy) has been found to play a critical role in human sensory neuropathy. So far, however, specific and efficient intervention means for ER-phagy remain unexplored. Herein, brefeldin A (BFA), a blocking agent on protein transport between the ER and Golgi, was screened from ER stress inducers. BFA was then delivered to the perinuclear area co-localized with the ER by a mesoporous silica nanoparticle-based drug-carrier functionalized with autophagy-inducing peptides of TAT-beclin 1 (MSNs-BFA), to evoke a perturbation of ER-phagy. The molecular mechanism of ER-phagy regulated by BFA was explored by biochemical evaluation including time-lapse live-cell fluorescence imaging. We found that MSNs-BFA treatment caused a lower mRNA/protein expression level of FAM134b even under a compensation of autophagic flux in U2OS cells, and resulted in ER-expansion. The fragmentation of the ER was blocked as a response to ER stress mediated by inactivation of the AKT/TSC/mTOR pathway. Our work developed an efficient external manipulation strategy to regulate ER-phagy and may contribute to the therapeutic application of autophagy-related major human diseases.
研究领域:
细胞生物学
·
分子生物学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）