14 research outputs found
Characterization of Apoptosis-Related Oxidoreductases from Neurospora crassa
The genome from Neurospora crassa presented three open reading frames homologous to the genes coding for human AIF and AMID proteins, which are flavoproteins with oxidoreductase activities implicated in caspase-independent apoptosis. To investigate the role of these proteins, namely within the mitochondrial respiratory chain, we studied their cellular localization and characterized the respective null mutant strains. Efficiency of the respiratory chain was analyzed by oxygen consumption studies and supramolecular organization of the OXPHOS system was assessed through BN-PAGE analysis in the respective null mutant strains. The results demonstrate that, unlike in mammalian systems, disruption of AIF in Neurospora does not affect either complex I assembly or function. Furthermore, the mitochondrial respiratory chain complexes of the mutant strains display a similar supramolecular organization to that observed in the wild type strain. Further characterization revealed that N. crassa AIF appears localized to both the mitochondria and the cytoplasm, whereas AMID was found exclusively in the cytoplasm. AMID2 was detected in both mitochondria and cytoplasm of the amid mutant strain, but was barely discernible in wild type extracts, suggesting overlapping functions for the two proteins
Lipid and elemental composition as indicators of the physiological state of sporangiospores in Mucor hiemalis cultures of different ages
Protein Kinase C Overexpression Suppresses Calcineurin-Associated Defects in Aspergillus nidulans and Is Involved in Mitochondrial Function
The contribution of Aspergillus fumigatus stress responses to virulence and antifungal resistance
Different Stress-Induced Calcium Signatures Are Reported by Aequorin-Mediated Calcium Measurements in Living Cells of Aspergillus fumigatus
Involvement of an Alternative Oxidase in Oxidative Stress and Mycelium-to-Yeast Differentiation in Paracoccidioides brasiliensis
Mitochondrial Respiratory Pathways Inhibition in Rhizopus oryzae Potentiates Activity of Posaconazole and Itraconazole via Apoptosis
The <i>Aspergillus fumigatus pkcA</i><sup>G579R</sup> Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model
<div><p><i>Aspergillus fumigatus</i> is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall homeostasis is controlled by the conserved <u>C</u>ell <u>W</u>all <u>I</u>ntegrity (CWI) pathway. In <i>A</i>. <i>fumigatus</i> this signaling cascade is partially characterized, but the mechanisms by which it is activated are not fully elucidated. In this study we investigated the role of protein kinase C (PkcA) in this signaling cascade. Our results suggest that <i>pkcA</i> is an essential gene and is activated in response to cell wall stress. Subsequently, we constructed and analyzed a non-essential <i>A</i>. <i>fumigatus pkcA</i><sup>G579R</sup> mutant, carrying a Gly579Arg substitution in the PkcA C1B regulatory domain. The <i>pkcA</i><sup>G579R</sup> mutation has a reduced activation of the downstream <u>M</u>itogen-<u>A</u>ctivated <u>P</u>rotein <u>K</u>inase, MpkA, resulting in the altered expression of genes encoding cell wall-related proteins, markers of endoplasmic reticulum stress and the unfolded protein response. Furthermore, PkcA<sup>G579R</sup> is involved in the formation of proper conidial architecture and protection to oxidative damage. The <i>pkcA</i><sup>G579R</sup> mutant elicits increased production of TNF-α and phagocytosis but it has no impact on virulence in a murine model of invasive pulmonary aspergillosis. These results highlight the importance of PkcA to the CWI pathway but also indicated that additional regulatory circuits may be involved in the biosynthesis and/or reinforcement of the <i>A</i>. <i>fumigatus</i> cell wall during infection.</p></div