Related Experiment Video
Updated: Jan 28, 2026

Measuring Diurnal Rhythms in Autophagic and Proteasomal Flux
Published on: September 17, 2019
Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux
Shaoyi Zhang1,2,3,4,5,6,7, Yan Wang3,4,5,6,7,8, Wei Xie2,3,4,5,6,7
1Department of Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Abstract:
Cystic fibrosis is a disease caused by defective function of a chloride channel coupled to a blockade of autophagic flux. It has been proposed to use synthetic chloride transporters as pharmacological agents to compensate insufficient chloride fluxes. Here, we report that such chloride anionophores block autophagic flux in spite of the fact that they activate the pro-autophagic transcription factor EB (TFEB) coupled to the inhibition of the autophagy-suppressive mTORC1 kinase activity. Two synthetic chloride transporters (SQ1 and SQ2) caused a partially TFEB-dependent relocation of the autophagic marker LC3 to the Golgi apparatus. Inhibition of TFEB activation using a calcium chelator or calcineurin inhibitors reduced the formation of LC3 puncta in cells, yet did not affect the cytotoxic action of SQ1 and SQ2 that could be observed after prolonged incubation. In conclusion, the squaramide-based synthetic chloride transporters studied in this work (which can also dissipate pH gradients) are probably not appropriate for the treatment of cystic fibrosis yet might be used for other indications such as cancer.
More Related Videos
07:47A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters
Published on: April 20, 2015
11:39Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry
Published on: July 21, 2017
Related Concept Videos
Secondary Active Transport
Secondary Active Transport
Primary Active Transport
Primary Active Transport
Active Transport
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...