Pinellia ternata lectin induces mitochondrial damage and inflammation in RAW264.7 cells via mannose receptor-mediated endocytosis.

Authors

Yangyi Huang, Jinfei Li, Yue Lu, Jie Cao, Xinzhi Wang, Hao Wu, Min Shen, Hongli Yu

Published in

Toxicology and applied pharmacology. Pages 117970. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

A lectin from Pinellia ternata tubers (PTL, 12 kDa) with potent pro-inflammatory activity binds to the plasma membrane and translocates into the cytoplasm. However, its cellular entry route and inflammatory toxicity mechanisms remain unclear. Here, confocal microscopy showed that fluorescein isothiocyanate (FITC)-labeled PTL (50 μg/mL) accumulated on the cell surface and was endocytosed by RAW264.7 cells time-dependently. Pharmacological inhibition revealed that PTL uptake was mediated by the mannose receptor C-type 2 (MRC2) and predominantly via clathrin-mediated endocytosis. After endocytosis, PTL translocated to mitochondria with marked co-localization, inducing mitochondrial damage characterized by membrane potential dissipation, calcium overload, and excessive mitochondrial reactive oxygen species (mtROS) generation. These alterations promoted intracellular ROS accumulation and amplified inflammatory responses. Co-immunoprecipitation with mass spectrometry identified ATP synthase subunit beta (ATP5B) as a mitochondrial interacting protein of PTL. Their interaction was validated by molecular docking, co-localization, and microscale thermophoresis (MST). ATP5B knockdown markedly attenuated PTL (50 μg/mL)-induced ROS production, inflammatory cytokine expression, and mitochondrial injury, indicating ATP5B is a critical mediator of PTL's inflammatory toxicity. Collectively, these findings demonstrate that PTL induces mitochondrial damage and pro-inflammatory responses in RAW264.7 cells through MRC2-mediated, clathrin-dependent endocytosis and subsequent ATP5B interaction. This study establishes a mechanistic link between lectin endocytosis, mitochondrial targeting, and inflammatory toxicity, providing new insight into plant lectin-mediated immunotoxicity.

PMID:
42498248
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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