Weihong Yang, Zhaoyang Wang, Xiangli Li, Dunji Shu, Yao He, Xinran Lian, Shuxin Sun, Xiaowei Feng, Xiaoyan Wu, Cheng Cui, Zhimin Wang, Hui Wu, Liping Qiu, Weihong Tan
The cellular positioning of lysosomes, especially their perinuclear accumulation, plays an essential role in regulating many biological processes. In this work, we developed a non-genetic approach to drive lysosomes to the perinuclear region by displaying a nucleus-targeting DNA nanodevice on their outer surface. Our experimental results demonstrated that this nanodevice efficiently anchored onto the outer leaflet of lysosomal membrane, and then effectively promoted perinuclear clustering of lysosomes. Further analysis revealed that this repositioning significantly enhanced autophagic flux and altered the expression of autophagy-associated genes. Our study provides a versatile platform for elucidating the functional consequences of lysosomal positioning and its regulatory mechanisms in cellular physiology.