Melittin triggers apoptosis in Candida albicans through the reactive oxygen species-mediated mitochondria/caspase-dependent pathway.
Melittin is one of the best-studied antimicrobial peptides, and many studies have focused on the membrane underlying its membrane-disruptive activity. We previously showed that melittin could cause some hallmarks of apoptosis in Candida albicans. Here, we first report the exact mechanism of melittin-induced fungal apoptosis. We first characterized the reactive oxygen species generated by melittin. The results showed that melittin strongly produced highly reactive hydroxyl radicals (˙OH), which contribute to cell death. Next, we showed that melittin also disrupted the mitochondrial membrane potential (ΔΨm) and induced the Ca(2+) release from the endoplasmic reticulum and its remarkable accumulation in mitochondria. Finally, we investigated the role of caspase in the apoptotic pathway. The results showed that melittin activated metacaspase, which was mediated by cytochrome c release. To summarize, melittin is involved in the mitochondria- and caspase-dependent apoptotic pathway in C. albicans. Our findings suggest that melittin possesses a dual antimicrobial mechanism, including membrane-disruptive and apoptotic actions.
School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daegu, Korea.
Juneyoung
J
Lee
Dong Gun
DG
Lee
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D008555:Melitten / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D017382:Reactive Oxygen Species; D008555:Melitten; D045304:Cytochromes c; D020169:Caspases; D002118:Calcium
antimicrobial peptide; fungal; programmed cell death