The Saccharomyces cerevisiae Genes, AIM45, YGR207c/CIR1 and YOR356w/ CIR2, Are Involved in Cellular Redox State Under Stress Conditions~!2010-06-02~!2010-06-21~!2010-08-16~!

Lopes, João P.P.B.; Pinto, Maria J.; Rodrigues, Aurora Corrêa; Vasconcelos, Filipe; Oliveira, Rui Pedro Soares de

doi:10.2174/1874285801004010075

Cited by 11 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support of this hypothesis, genes such as CAT 1, CAT 3 and TRR 1, known to be important for oxidative stress either in C. neoformans or in other fungal species were found to be up-regulated at three or more time points. The C. neoformans homologs of the S. cerevisiae genes ALD 5, ZTA 1, SCS 7 and CIR 2 were also induced at a minimum of three time points (Table S5) and deletion of these genes in S. cerevisiae has demonstrated their increased sensitivity to oxidative stress [41], [42], [43].…”

Section: Resultsmentioning

confidence: 99%

Global Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative Stress

et al. 2013

View full text Add to dashboard Cite

The ability of the opportunistic fungal pathogen Cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. To cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macrophages, C. neoformans has developed multilayered redundant molecular responses to neutralize the stress, to repair the damage and to eventually grow inside the hostile environment of the phagosome. We used microarray analysis of cells treated with hydrogen peroxide (H2O2) at multiple time points in a nutrient defined medium to identify a transcriptional signature associated with oxidative stress. We discovered that the composition of the medium in which fungal cells were grown and treated had a profound effect on their capacity to degrade exogenous H2O2. We determined the kinetics of H2O2 breakdown by growing yeast cells under different conditions and accordingly selected an appropriate media composition and range of time points for isolating RNA for hybridization. Microarray analysis revealed a robust transient transcriptional response and the intensity of the global response was consistent with the kinetics of H2O2 breakdown by treated cells. Gene ontology analysis of differentially expressed genes related to oxidation-reduction, metabolic process and protein catabolic processes identified potential roles of mitochondrial function and protein ubiquitination in oxidative stress resistance. Interestingly, the metabolic pathway adaptation of C. neoformans to H2O2 treatment was remarkably distinct from the response of other fungal organisms to oxidative stress. We also identified the induction of an antifungal drug resistance response upon the treatment of C. neoformans with H2O2. These results highlight the complexity of the oxidative stress response and offer possible new avenues for improving our understanding of mechanisms of oxidative stress resistance in C. neoformans.

show abstract

Section: Resultsmentioning

confidence: 99%

Global Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative Stress

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Unfortunately, other flavoenzymes, which are expected to be altered in MADD/LSMFLAD/RREI, were not assayed in yeast models. In particular, data are missing concerning the system ETFα/ETFβ/ETF-QO, which are mitochondrially located and encoded by AIM45 , CIR1 and CIR2 in S. cerevisiae , whose alteration can be a cause of ROS unbalance [ 162 , 177 , 178 ]. Conversely, the activity/level of lipoamide dehydrogenase—a component of enzymatic complexes that decarboxylate pyruvate, oxoglutarate and oxoacids deriving from branched-chain amino acids—was not tested, as well as that of ETF/ETF-QO has not yet been investigated in RREI patients’ cells.…”

Section: Model Organisms To Study Flavin Homeostasis Alterationsmentioning

confidence: 99%

Development of Novel Experimental Models to Study Flavoproteome Alterations in Human Neuromuscular Diseases: The Effect of Rf Therapy

Tolomeo

Nisco

Leone

et al. 2020

IJMS

View full text Add to dashboard Cite

Inborn errors of Riboflavin (Rf) transport and metabolism have been recently related to severe human neuromuscular disorders, as resulting in profound alteration of human flavoproteome and, therefore, of cellular bioenergetics. This explains why the interest in studying the “flavin world”, a topic which has not been intensively investigated before, has increased much over the last few years. This also prompts basic questions concerning how Rf transporters and FAD (flavin adenine dinucleotide) -forming enzymes work in humans, and how they can create a coordinated network ensuring the maintenance of intracellular flavoproteome. The concept of a coordinated cellular “flavin network”, introduced long ago studying humans suffering for Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), has been, later on, addressed in model organisms and more recently in cell models. In the frame of the underlying relevance of a correct supply of Rf in humans and of a better understanding of the molecular rationale of Rf therapy in patients, this review wants to deal with theories and existing experimental models in the aim to potentiate possible therapeutic interventions in Rf-related neuromuscular diseases.

show abstract

“…In some cases, however, ETF is part of a specialized system, for example, in Methylophilus methylotrophus and Peptostreptococcus elsdenii. The cellular role of the electron-transferring flavoprotein of Saccharomyces cerevisiae (yETF) appears to be similar to bacterial homologs because only one enzyme is currently suspected to deliver electrons, that is, D-lactate dehydrogenase (Dld2), whereas yETF was reported to deliver the electrons to an ETF-QO homolog, named Cir2p, and thus shares this feature with other eukaryotic organisms [11,12]. In other cases, reduced ETFs transfer electrons to acyl-CoA dehydrogenases, which subsequently catalyze the reduction in short-chain a,b-unsaturated fatty acids [8].…”

Section: Introductionmentioning

confidence: 99%

“…In other cases, reduced ETFs transfer electrons to acyl-CoA dehydrogenases, which subsequently catalyze the reduction in short-chain a,b-unsaturated fatty acids [8]. The cellular role of the electron-transferring flavoprotein of Saccharomyces cerevisiae (yETF) appears to be similar to bacterial homologs because only one enzyme is currently suspected to deliver electrons, that is, D-lactate dehydrogenase (Dld2), whereas yETF was reported to deliver the electrons to an ETF-QO homolog, named Cir2p, and thus shares this feature with other eukaryotic organisms [11,12].…”

Section: Introductionmentioning

confidence: 99%

Closing the gap: yeast electron‐transferring flavoprotein links the oxidation of d‐lactate and d‐α‐hydroxyglutarate to energy production via the respiratory chain

et al. 2019

View full text Add to dashboard Cite

Electron‐transferring flavoproteins (ETFs) have been found in all kingdoms of life, mostly assisting in shuttling electrons to the respiratory chain for ATP production. While the human (h) ETF has been studied in great detail, very little is known about the biochemical properties of the homologous protein in the model organism Saccharomyces cerevisiae (yETF). In view of the absence of client dehydrogenases, for example, the acyl‐CoA dehydrogenases involved in the β‐oxidation of fatty acids, d‐lactate dehydrogenase 2 (Dld2) appeared to be the only relevant enzyme that is serviced by yETF for electron transfer to the mitochondrial electron transport chain. However, this hypothesis was never tested experimentally. Here, we report the biochemical properties of yETF and Dld2 as well as the electron transfer reaction between the two proteins. Our study revealed that Dld2 oxidizes d‐α‐hydroxyglutarate more efficiently than d‐lactate exhibiting kcatapp/KMapp values of 1200 ± 300 m−1·s−1 and 11 ± 2 m−1·s−1, respectively. As expected, substrate‐reduced Dld2 very slowly reacted with oxygen or the artificial electron acceptor 2,6‐dichlorophenol indophenol. However, photoreduced Dld2 was rapidly reoxidized by oxygen, suggesting that the reaction products, that is, α‐ketoglutarate and pyruvate, ‘lock’ the reduced enzyme in an unreactive state. Interestingly, however, we could demonstrate that substrate‐reduced Dld2 rapidly transfers electrons to yETF. Therefore, we conclude that the formation of a product‐reduced Dld2 complex suppresses electron transfer to dioxygen but favors the rapid reduction in yETF, thus preventing the loss of electrons and the generation of reactive oxygen species.

show abstract

The Saccharomyces cerevisiae Genes, AIM45, YGR207c/CIR1 and YOR356w/ CIR2, Are Involved in Cellular Redox State Under Stress Conditions~!2010-06-02~!2010-06-21~!2010-08-16~!

Cited by 11 publications

References 27 publications

Global Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative Stress

Global Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative Stress

Development of Novel Experimental Models to Study Flavoproteome Alterations in Human Neuromuscular Diseases: The Effect of Rf Therapy

Closing the gap: yeast electron‐transferring flavoprotein links the oxidation of d‐lactate and d‐α‐hydroxyglutarate to energy production via the respiratory chain

Contact Info

Product

Resources

About