Open AccessHonokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans
Author(s) -
Libo Sun,
Kai Liao,
Dayong Wang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184003
Subject(s) - honokiol , mitochondrial respiratory chain , superoxide , reactive oxygen species , respiratory chain , mitochondrion , oxidative stress , biology , biochemistry , magnolia officinalis , rotenone , oxidative phosphorylation , chemistry , pharmacology , microbiology and biotechnology , enzyme , medicine , alternative medicine , traditional chinese medicine , pathology
Background Honokiol, a compound extracted from Magnolia officinalis , has antifungal activities by inducing mitochondrial dysfunction and triggering apoptosis in Candida albicans . However, the mechanism of honokiol-induced oxidative stress is poorly understood. The present investigation was designed to determine the specific mitochondrial reactive oxygen species (ROS)-generation component. Methods/results We found that honokiol induced mitochondrial ROS accumulation, mainly superoxide anions (O 2 •− ) measured by fluorescent staining method. The mitochondrial respiratory chain complex I (C I) inhibitor rotenone completely blocked O 2 •− production and provided the protection from the killing action of honokiol. Moreover, respiratory activity and the C I enzyme activity was significantly reduced after honokiol treatment. The differential gene-expression profile also showed that genes involved in oxidoreductase activity, electron transport, and oxidative phosphorylation were upregulated. Conclusions The present work shows that honokiol may bind to mitochondrial respiratory chain C I, leading to mitochondrial dysfunction, accompanied by increased cellular superoxide anion and oxidative stress. General significance This work not only provides insights on the mechanism by which honokiol interferes with fungal cell, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of M . officinalis as a Chinese medicine due to the toxic for mitochondria and suggests the possibility of using honokiol as chemosensitizer.