Thorium inhibits human respiratory chain complex IV (cytochrome c oxidase).

Abstract

Thorium is a radioactive heavy metal and an emerging environmental pollutant. Ecological and human health risks from thorium exposure are growing with the excavation of rare earth metals and implementation of thorium-based nuclear reactors. Thorium poisoning is associated with carcinogenesis, liver impairments, and congenital anomalies. To date, the biomolecular targets that underlie thorium-induced toxicity remain unknown. Here, we used in vitro enzymatic activity assays to comprehensively evaluate the effects of thorium on the mitochondrial respiration process. Thorium was found to inhibit respiratory chain complex IV (cytochrome c oxidase) at sub-micromolar concentrations (IC50 ~ 0.4 μM, 90 μg/L). This is lower than the thorium level limit (246 μg/L) in drinking water specified by the World Health Organization. The inhibitory effects were further verified in mitochondria from human bone and liver cells (thorium mainly deposits in these organs). The inhibition of cytochrome c oxidase can readily rationalize well-documented cellular toxicities of thorium, such as alteration of mitochondrial membrane potential and production of reactive oxygen species. Therefore, cytochrome c oxidase is potentially a key molecular target underlying thorium-induced toxicological effect.

• Authors: Libing Yu, Zhaozhu Lin, Xuedan Cheng, Jian Chu, Xijian Li, Chun Chen, Tinghua Zhu, Wenjing Li, Wei Lin, Wei Tang
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 424 Issue Pt B Pg. 127546 (02 15 2022) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 34879532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Thorium
• Electron Transport Complex IV

Topics

• Electron Transport
• Electron Transport Complex IV (metabolism)
• Humans
• Membrane Potential, Mitochondrial
• Mitochondria (metabolism)
• Thorium (metabolism)