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Lactoferricin B like peptide triggers mitochondrial disruption‐mediated apoptosis by inhibiting respiration under nitric oxide accumulation in Candida albicans
Author(s) -
Kim Suhyun,
Hwang Jae Sam,
Lee Dong Gun
Publication year - 2020
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2284
Subject(s) - candida albicans , intracellular , nitric oxide , mitochondrion , glutathione , apoptosis , biochemistry , corpus albicans , superoxide , biology , oxidative stress , microbiology and biotechnology , chemistry , enzyme , endocrinology
Nitric oxide (NO) is a potentially powerful weapon against Candida albicans , and the regulation of intracellular NO levels is therefore important for controlling its physiological functions. Lactoferricin B like peptide (LBLP) is a 23‐mer antimicrobial peptide (AMP) derived from the Scolopendra subspinipes mutilans . We confirmed that LBLP treatment led to the generation of endogenous NO in C. albicans , which was associated with the NO synthase pathway. Here, we examined the antifungal activity of LBLP with focus on intracellular NO. Total glutathione levels were measured to evaluate cellular defense capacity against NO. LBLP decreased total glutathione levels, leading to nitrosative stress. LBLP also inhibited mitochondrial respiration and altered the NAD +/ NADH ratios. Inhibition of mitochondrial respiration induced mitochondrial membrane depolarization, thus leading to calcium homeostasis disruption and mitochondrial superoxide anion accumulation. Consequently, treatment of C. albicans with LBLP resulted in apoptosis. These physiological changes were attenuated when NO generation was inhibited. Our data strongly indicate that LBLP mediates apoptosis by affecting intracellular NO homeostasis. These results on antifungal activity of LBLP and its mechanism indicate the therapeutic promise of this AMP and support the role of NO in cell death regulation.