The metacaspase (Mca1p) has a dual role in farnesol-induced apoptosis in Candida albicans.
Mol Cell Proteomics
; 14(1): 93-108, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25348831
ABSTRACT
Manipulating the apoptotic response of Candida albicans may help in the control of this opportunistic pathogen. The metacaspase Mca1p has been described as a key protease for apoptosis in C. albicans but little is known about its cleavage specificity and substrates. We therefore initiated a series of studies to describe its function. We used a strain disrupted for the MCA1 gene (mca1Δ/Δ) and compared its proteome to that of a wild-type isogenic strain, in the presence and absence of a known inducer of apoptosis, the quorum-sensing molecule farnesol. Label-free and TMT labeling quantitative proteomic analyses showed that both mca1 disruption and farnesol treatment significantly affected the proteome of the cells. The combination of both conditions led to an unexpected biological response the strong overexpression of proteins implicated in the general stress. We studied sites cleaved by Mca1p using native peptidomic techniques, and a bottom-up approach involving GluC endoprotease there appeared to be a "K/R" substrate specificity in P1 and a "D/E" specificity in P2. We also found 77 potential substrates of Mca1p, 13 of which validated using the most stringent filters, implicated in protein folding, protein aggregate resolubilization, glycolysis, and a number of mitochondrial functions. An immunoblot assay confirmed the cleavage of Ssb1p, a member of the HSP70 family of heat-shock proteins, in conditions where the metacaspase is activated. These various results indicate that Mca1p is involved in a limited and specific proteolysis program triggered by apoptosis. One of the main functions of Mca1p appears to be the degradation of several major heat-shock proteins, thereby contributing to weakening cellular defenses and amplifying the cell death process. Finally, Mca1p appears to contribute significantly to the control of mitochondria biogenesis and degradation. Consequently, Mca1p may be a link between the extrinsic and the intrinsic programmed cell death pathways in C. albicans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Candida albicans
/
Proteínas Fúngicas
/
Apoptose
/
Caspases
Idioma:
En
Revista:
Mol Cell Proteomics
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2015
Tipo de documento:
Article