Plagiochin E, an antifungal bis(bibenzyl), exerts its antifungal activity through mitochondrial dysfunction-induced reactive oxygen species accumulation in Candida albicans.
BACKGROUND
Plagiochin E (PLE) is an antifungal macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L. Its antifungal mechanism is unknown. To elucidate the mechanism of action, its effect on mitochondria function in Candida albicans was studied.


METHODS
We assayed the mitochondrial membrane potential (mtDeltapsi) using rhodamine 123, measured ATP level in mitochondria by HPLC, and detected the activities of mitochondrial F(0)F(1)-ATPase and dehydrogenases. Besides, the mitochondrial dysfunction-induced reactive oxygen species (ROS) production was determined by a fluorometric assay, and the effects of antioxidant L-cysteine on PLE-induced ROS production and the antifungal effect of PLE on C. albicans were also investigated.


RESULTS
Exposure to PLE resulted in an elevation of mtDeltapsi, and a decrease of ATP level in mitochondria. The ATP depletion owed to PLE-induced enhancement of mitochondrial F(0)F(1)-ATPase and inhibition of the mitochondrial dehydrogenases. These dysfunctions of mitochondria caused ROS accumulation in C. albicans, and this increase in the level of ROS production and PLE-induced decrease in cell viability were prevented by addition of L-cysteine, indicating that ROS was an important mediator of the antifungal action of PLE.


CONCLUSIONS
PLE exerts its antifungal activity through mitochondrial dysfunction-induced ROS accumulation in C. albicans.


CONCLUSIONS
The effect of PLE on the mitochondria function in C. albicans was assayed for the first time. These results would conduce to elucidate its underlying antifungal mechanism.
Wu
Xiu-Zhen
XZ
School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, PR China.
Cheng
Ai-Xia
AX
Sun
Ling-Mei
LM
Sun
Shu-Juan
SJ
Lou
Hong-Xiang
HX
D000143:Acids / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001632:Bibenzyls / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003545:Cysteine / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
D000143:Acids; D000935:Antifungal Agents; D000975:Antioxidants; D001632:Bibenzyls; D001952:Bridged-Ring Compounds; D017382:Reactive Oxygen Species; D013267:Stilbenes; C529889:plagiochin E; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D006180:Proton-Translocating ATPases; D005947:Glucose; D003545:Cysteine