Study finds plant alkaloid triggers unique two-phase response in cell cleanup process

Sadie Harley
scientific editor

Andrew Zinin
lead editor

Researchers at the University of Tsukuba have discovered a unique biphasic cellular response triggered by tetrandrine, a naturally occurring alkaloid containing nitrogen. The research is in the journal ACS Chemical Biology.
Autophagy is a mechanism whereby unnecessary proteins and organelles within cells are removed, often called a "cellular cleaning crew." Lysosomes, small organelles within cells, play a key role in this process.
Tetrandrine, a nitrogen-containing alkaloid primarily found in Stephania tetrandra, a plant native to China and Taiwan, can modulate autophagy and has various pharmacological activities, including anticancer and neuroprotective effects. However, the detailed mechanism underlying these functions, particularly its role in autophagy, remains unclear.
In this study, researchers investigated the subcellular tetrandrine localization using a fluorescently tagged compound, Probe 2. They found that Probe 2 specifically accumulated in lysosomes.
Furthermore, tetrandrine temporarily increased the pH in lysosomes, which are normally acidic, thereby inhibiting their function. The researchers discovered that tetrandrine triggers a two-step cellular response wherein damaged lysosomes are selectively removed by autophagy (lysophagy) while promoting the formation of new lysosomes.
Unlike existing modulators that target lysosomes by blocking membrane channels or inhibiting intralysosomal hydrolases, tetrandrine triggers a unique cellular response, highlighting its therapeutic potential in autophagy-lysosome dysfunction diseases such as neurodegeneration.
More information: Zhe Yang et al, Biphasic Cellular Response Triggered by Tetrandrine-Mediated Dysfunction and Lysophagic Clearance of Lysosomes, ACS Chemical Biology (2025).
Journal information: ACS Chemical Biology
Provided by University of Tsukuba