Real-time tracking of ER turnover during ERLAD by a rhenium complex via lifetime imaging

Liang Hao; Yu-Yi Ling; Zhi-Xin Huang; Zheng-Yin Pan; Cai-Ping Tan; Zong-Wan Mao

doi:10.1093/nsr/nwab194

Real-time tracking of ER turnover during ERLAD by a rhenium complex via lifetime imaging

Natl Sci Rev. 2021 Oct 28;9(7):nwab194. doi: 10.1093/nsr/nwab194. eCollection 2022 Jul.

Authors

Liang Hao¹, Yu-Yi Ling¹, Zhi-Xin Huang¹, Zheng-Yin Pan¹, Cai-Ping Tan¹, Zong-Wan Mao¹

Affiliation

¹ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou 510275, China.

Abstract

Endoplasmic reticulum (ER) degradation by autophagy (ER-phagy) is a recently revealed selective autophagy pathway that plays important roles in organelle turnover and protein degradation, but the biological functions of ER-phagy are largely unknown. Here, we present an ER-targeting Re(I) tricarbonyl complex (Re-ERLAD) that can accumulate in the ER, induce ER-to-lysosome-associated degradation (ERLAD) upon visible light irradiation, and label ER buds and track their morphological alterations during ER-phagy. The emission of Re-ERLAD is sensitive to viscosity, which is a key parameter reflecting the amount of unfolded protein in the ER. Quantitative detection using two-photon fluorescence lifetime imaging microscopy shows that ER viscosity initially increases and then decreases during ERLAD, which reveals that ERLAD is a pathway for alleviating ER stress caused by unfolded proteins. In conclusion, our work presents the first specific photoinducer and tracker of ERLAD, which can be used in studying the regulatory mechanism and function of this process.

Keywords: ER-phagy; TPFLIM; rhenium; viscosity.