scholarly journals The F1Fo-ATP Synthase β Subunit Is Required for Candida albicans Pathogenicity Due to Its Role in Carbon Flexibility

2018 ◽  
Vol 9 ◽  
Author(s):  
Shui-Xiu Li ◽  
Hao-Tian Wu ◽  
Yu-Ting Liu ◽  
Yi-Ying Jiang ◽  
Yi-Shan Zhang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Atp Synthase ◽  
Β Subunit ◽  
F1fo Atp Synthase

The fungal-specific subunit i/j of F1FO-ATP synthase stimulates the pathogenicity of Candida albicans independent of oxidative phosphorylation

2020 ◽  
Author(s):  
Yajing Zhao ◽  
Yan Lyu ◽  
Yanli Zhang ◽  
Shuixiu Li ◽  
Yishan Zhang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Fungal Infections ◽  
Critical Role ◽  
Antifungal Drug ◽  
F1fo Atp Synthase

Abstract Invasive fungal infections are a major cause of human mortality due in part to a very limited antifungal drug arsenal. The identification of fungal-specific pathogenic mechanisms is considered a crucial step to current antifungal drug development and represents a significant goal to increase the efficacy and reduce host toxicity. Although the overall architecture of F1FO-ATP synthase is largely conserved in both fungi and mammals, the subunit i/j (Su i/j, Atp18) and subunit k (Su k, Atp19) are proteins not found in mammals and specific to fungi. Here, the role of Su i/j and Su k in Candida albicans was characterized by an in vivo assessment of the virulence and in vitro growth and mitochondrial function. Strikingly, the atp18Δ/Δ mutant showed significantly reduced pathogenicity in systemic murine model. However, this substantial defect in infectivity exists without associated defects in mitochondrial oxidative phosphorylation or proliferation in vitro. Analysis of virulence-related traits reveals normal in both mutants, but shows cell wall defects in composition and architecture in the case of atp18Δ/Δ. We also find that the atp18Δ/Δ mutant is more susceptible to attack by macrophages than wild type, which may correlate well with the abnormal cell wall function and increased sensitivity to oxidative stress. In contrast, no significant changes were observed in any of these studies for the atp19Δ/Δ. These results demonstrate that the fungal-specific Su i/j, but not Su k of F1FO-ATP synthase may play a critical role in C. albicans infectivity and represent another opportunity for new therapeutic target investigation. Lay Abstract This study aims to investigate biological functions of fungal-specific subunit i/j and subunit k of ATP synthase in C. albicans oxidative phosphorylation and virulence potential. Our results revealed that subunit i/j, and not subunit k, is critical for C. albicans pathogenicity.

scholarly journals The F1Fo-ATP Synthase of Mycobacterium smegmatis Is Essential for Growth

2005 ◽  
Vol 187 (14) ◽  
pp. 5023-5028 ◽  
Author(s):  
Sieu L. Tran ◽  
Gregory M. Cook
Keyword(s):  
Atp Synthase ◽  
Mycobacterium Smegmatis ◽  
Essential Gene ◽  
Carbon Sources ◽  
Β Subunit ◽  
F1fo Atp Synthase ◽  
Cellular Processes

ABSTRACT The F1Fo-ATP synthase plays an important role in a number of vital cellular processes in plants, animals, and microorganisms. In this study, we constructed a ΔatpD mutant of Mycobacterium smegmatis and demonstrated that atpD encoding the β subunit of the F1Fo-ATP synthase is an essential gene in M. smegmatis during growth on nonfermentable and fermentable carbon sources.

Deletion of the natural inhibitory protein Inh1 in Ustilago maydis has no effect on the dimeric state of the F1FO-ATP synthase but increases the ATPase activity and reduces the stability

2021 ◽  
Vol 1862 (7) ◽  
pp. 148429
Author(s):  
Romero-Aguilar Lucero ◽  
Esparza-Perusquía Mercedes ◽  
Langner Thorsten ◽  
García-Cruz Giovanni ◽  
Feldbrügge Michael ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Atp Synthase ◽  
Ustilago Maydis ◽  
Inhibitory Protein ◽  
F1fo Atp Synthase ◽  
The Stability

scholarly journals Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 242
Author(s):  
Salvatore Nesci ◽  
Fabiana Trombetti ◽  
Alessandra Pagliarani ◽  
Vittoria Ventrella ◽  
Cristina Algieri ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Ros Generation ◽  
Protonmotive Force ◽  
Mitochondrial Oxidative Phosphorylation ◽  
F1fo Atp Synthase ◽  
Functional Changes ◽  
Age Related ◽  
Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

scholarly journals The spatio-temporal organization of mitochondrial F1FO ATP synthase in cristae depends on its activity mode

2020 ◽  
Vol 1861 (1) ◽  
pp. 148091 ◽  
Author(s):  
Kirill Salewskij ◽  
Bettina Rieger ◽  
Frances Hager ◽  
Tasnim Arroum ◽  
Patrick Duwe ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Temporal Organization ◽  
F1fo Atp Synthase ◽  
Activity Mode ◽  
Spatio Temporal

Influence of thyroid hormones on the human ATP synthase β-subunit gene promoter

1996 ◽  
Vol 154 (2) ◽  
pp. 107-111 ◽  
Author(s):  
Immaculada Martin ◽  
Josep A. Villena ◽  
Marta Giralt ◽  
Roser Iglesias ◽  
Teresa Mampel ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Atp Synthase ◽  
Gene Promoter ◽  
Β Subunit ◽  
Subunit Gene

scholarly journals Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL

2000 ◽  
Vol 20 (9) ◽  
pp. 3125-3136 ◽  
Author(s):  
Atan Gross ◽  
Kirsten Pilcher ◽  
Elizabeth Blachly-Dyson ◽  
Emy Basso ◽  
Jennifer Jockel ◽  
...  
Keyword(s):  
Cell Death ◽  
Mitochondrial Genome ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Family Members ◽  
Growth Arrest ◽  
Anion Channel ◽  
Cell Killing ◽  
Β Subunit ◽  
Voltage Dependent Anion Channel

ABSTRACT The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) and antiapoptotic (e.g., BCL-2 and BCL-XL) molecules. The cell death-regulating activity of BCL-2 members appears to depend on their ability to modulate mitochondrial function, which may include regulation of the mitochondrial permeability transition pore (PTP). We examined the function of BAX and BCL-XL using genetic and biochemical approaches in budding yeast because studies with yeast suggest that BCL-2 family members act upon highly conserved mitochondrial components. In this study we found that in wild-type yeast, BAX induced hyperpolarization of mitochondria, production of reactive oxygen species, growth arrest, and cell death; however, cytochrome c was not released detectably despite the induction of mitochondrial dysfunction. Coexpression of BCL-XL prevented all BAX-mediated responses. We also assessed the function of BCL-XL and BAX in the same strain of Saccharomyces cerevisiae with deletions of selected mitochondrial proteins that have been implicated in the function of BCL-2 family members. BAX-induced growth arrest was independent of the tested mitochondrial components, including voltage-dependent anion channel (VDAC), the catalytic β subunit or the δ subunit of the F0F1-ATP synthase, mitochondrial cyclophilin, cytochrome c, and proteins encoded by the mitochondrial genome as revealed by [rho 0] cells. In contrast, actual cell killing was dependent upon select mitochondrial components including the β subunit of ATP synthase and mitochondrial genome-encoded proteins but not VDAC. The BCL-XL protection from either BAX-induced growth arrest or cell killing proved to be independent of mitochondrial components. Thus, BAX induces two cellular processes in yeast which can each be abrogated by BCL-XL: cell arrest, which does not require aspects of mitochondrial biochemistry, and cell killing, which does.

scholarly journals Epigenetic control of pheromone MAPK signaling determines sexual fecundity inCandida albicans

2017 ◽  
Vol 114 (52) ◽  
pp. 13780-13785 ◽  
Author(s):  
Christine M. Scaduto ◽  
Shail Kabrawala ◽  
Gregory J. Thomson ◽  
William Scheving ◽  
Andy Ly ◽  
...  
Keyword(s):  
Candida Albicans ◽  
G Protein ◽  
Map Kinases ◽  
Mapk Pathway ◽  
Cell Types ◽  
Mapk Signaling ◽  
Toggle Switch ◽  
Β Subunit ◽  
Epigenetic Control ◽  
Incandida Albicans

Several pathogenicCandidaspecies are capable of heritable and reversible switching between two epigenetic states, “white” and “opaque.” InCandida albicans, white cells are essentially sterile, whereas opaque cells are mating-proficient. Here, we interrogate the mechanism by which the white-opaque switch regulates sexual fecundity and identify four genes in the pheromone MAPK pathway that are expressed at significantly higher levels in opaque cells than in white cells. These genes encode the β subunit of the G-protein complex (STE4), the pheromone MAPK scaffold (CST5), and the two terminal MAP kinases (CEK1/CEK2). To define the contribution of each factor to mating,C. albicanswhite cells were reverse-engineered to express elevated, opaque-like levels of these factors, either singly or in combination. We show that white cells co-overexpressingSTE4,CST5, andCEK2undergo mating four orders of magnitude more efficiently than control white cells and at a frequency approaching that of opaque cells. Moreover, engineered white cells recapitulate the transcriptional and morphological responses of opaque cells to pheromone. These results therefore reveal multiple bottlenecks in pheromone MAPK signaling in white cells and that alleviation of these bottlenecks enables efficient mating by these “sterile” cell types. Taken together, our findings establish that differential expression of several MAPK factors underlies the epigenetic control of mating inC. albicans. We also discuss how fitness advantages could have driven the evolution of a toggle switch to regulate sexual reproduction in pathogenicCandidaspecies.

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