scholarly journals The mitochondrial copper chaperone COX11 has an additional role in cellular redox homeostasis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261465
Author(s):  
Ivan Radin ◽  
Luise Kost ◽  
Uta Gey ◽  
Iris Steinebrunner ◽  
Gerhard Rödel
Keyword(s):  
Redox Homeostasis ◽  
Normal Growth ◽  
Yeast Cells ◽  
Flowering Plant ◽  
Cellular Respiration ◽  
Copper Chaperone ◽  
Complex Assembly ◽  
Cellular Redox ◽  
Knock Out ◽  
Defensive Role

Mitochondria are sites of cellular respiration, which is accompanied by the generation of dangerous reactive oxygen species (ROS). Cells have multiple mechanisms to mitigate the dangers of ROS. Here we investigate the involvement of the COX complex assembly chaperone COX11 (cytochrome c oxidase 11) in cellular redox homeostasis, using homologs from the flowering plant Arabidopsis thaliana (AtCOX11) and yeast Saccharomyces cerevisiae (ScCOX11). We found that AtCOX11 is upregulated in Arabidopsis seedlings in response to various oxidative stresses, suggesting a defensive role. In line with this, the overexpression of either AtCOX11 or ScCOX11 reduced ROS levels in yeast cells exposed to the oxidative stressor paraquat. Under normal growth conditions, both Arabidopsis and yeast COX11 overexpressing cells had the same ROS levels as the corresponding WT. In contrast, the COX11 knock-down and knock-out in Arabidopsis and yeast, respectively, significantly reduced ROS levels. In yeast cells, the ScCOX11 appears to be functionally redundant with superoxide dismutase 1 (ScSOD1), a superoxide detoxifying enzyme. The ΔSccox11ΔScsod1 mutants had dramatically reduced growth on paraquat, compared with the WT or single mutants. This growth retardation does not seem to be linked to the status of the COX complex and cellular respiration. Overexpression of putatively soluble COX11 variants substantially improved the resistance of yeast cells to the ROS inducer menadione. This shows that COX11 proteins can provide antioxidative protection likely independently from their COX assembly function. The conserved Cys219 (in AtCOX11) and Cys208 (in ScCOX11) are important for this function. Altogether, these results suggest that COX11 homologs, in addition to participating in COX complex assembly, have a distinct and evolutionary conserved role in protecting cells during heightened oxidative stress.

scholarly journals Temporal profiling of redox-dependent heterogeneity in single cells

2017 ◽  
Author(s):  
Meytal Radzinski ◽  
Rosi Fasler ◽  
Ohad Yogev ◽  
William Breuer ◽  
Nadav Shai ◽  
...  
Keyword(s):  
Single Cells ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Yeast Cells ◽  
Protein Homeostasis ◽  
Cellular Functions ◽  
Defense Proteins ◽  
Cellular Redox ◽  
Oxidation Status ◽  
Logarithmic Growth

AbstractCellular redox status affects diverse cellular functions, including proliferation, protein homeostasis, and aging. Thus, individual differences in redox status can give rise to distinct sub-populations even among cells with identical genetic backgrounds. Here, we have created a novel methodology to track redox status at single cell resolution using the redox-sensitive probe roGFP. Our method allows identification and sorting of sub-populations with different oxidation levels in either the cytosol, mitochondria or peroxisomes. Using this approach we defined redox-dependent heterogeneity of yeast cells, and characterized growth, as well as proteomic and transcriptomic profiles of subpopulations of cells that differ in their redox status, but are similar in age. We report that, starting in late logarithmic growth, cells of the same age have a bi-modal distribution of oxidation status. A comparative proteomic analysis between these populations identified three key proteins, Hsp30, Dhh1, and Pnc1, which affect basal oxidation levels and may serve as first line of defense proteins in redox homeostasis.

scholarly journals Time line of redox events in aging postmitotic cells

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Nicolas Brandes ◽  
Heather Tienson ◽  
Antje Lindemann ◽  
Victor Vitvitsky ◽  
Dana Reichmann ◽  
...  
Keyword(s):  
Redox Homeostasis ◽  
Yeast Cells ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Cellular Redox ◽  
Time Line ◽  
Present Evidence ◽  
Cellular Processes ◽  
Theory Of Aging ◽  
Substantial Drop

The precise roles that oxidants play in lifespan and aging are still unknown. Here, we report the discovery that chronologically aging yeast cells undergo a sudden redox collapse, which affects over 80% of identified thiol-containing proteins. We present evidence that this redox collapse is not triggered by an increase in endogenous oxidants as would have been postulated by the free radical theory of aging. Instead it appears to be instigated by a substantial drop in cellular NADPH, which normally provides the electron source for maintaining cellular redox homeostasis. This decrease in NADPH levels occurs very early during lifespan and sets into motion a cascade that is predicted to down-regulate most cellular processes. Caloric restriction, a near-universal lifespan extending measure, increases NADPH levels and delays each facet of the cascade. Our studies reveal a time line of events leading up to the system-wide oxidation of the proteome days before cell death.

scholarly journals Temporal profiling of redox-dependent heterogeneity in single cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Meytal Radzinski ◽  
Rosi Fassler ◽  
Ohad Yogev ◽  
William Breuer ◽  
Nadav Shai ◽  
...  
Keyword(s):  
Single Cells ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Yeast Cells ◽  
Protein Homeostasis ◽  
Cellular Functions ◽  
Defense Proteins ◽  
Cellular Redox ◽  
Oxidation Status ◽  
Logarithmic Growth

Cellular redox status affects diverse cellular functions, including proliferation, protein homeostasis, and aging. Thus, individual differences in redox status can give rise to distinct sub-populations even among cells with identical genetic backgrounds. Here, we have created a novel methodology to track redox status at single cell resolution using the redox-sensitive probe Grx1-roGFP2. Our method allows identification and sorting of sub-populations with different oxidation levels in either the cytosol, mitochondria or peroxisomes. Using this approach, we defined a redox-dependent heterogeneity of yeast cells and characterized growth, as well as proteomic and transcriptomic profiles of distinctive redox subpopulations. We report that, starting in late logarithmic growth, cells of the same age have a bi-modal distribution of oxidation status. A comparative proteomic analysis between these populations identified three key proteins, Hsp30, Dhh1, and Pnc1, which affect basal oxidation levels and may serve as first line of defense proteins in redox homeostasis.

Mitochondria-Targeted Ratiometric Fluorescent Imaging of Cysteine

The Analyst ◽  
2021 ◽  
Author(s):  
Ya-Nan Wei ◽  
Bo Lin ◽  
Yang Shu ◽  
Jian-Hua Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Homeostasis ◽  
Reactive Oxygen ◽  
Fluorescent Imaging ◽  
Oxygen Species ◽  
Cellular Redox ◽  
Critical Part ◽  
Physiological Processes

As an indispensable biothiol, cysteine (Cys) plays a critical part in cellular redox homeostasis, pathological and physiological processes. One of the main sources of reactive oxygen species (ROS) in human...

scholarly journals Micro RNAs in Regulation of Cellular Redox Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6022
Author(s):  
Sylwia Ciesielska ◽  
Izabella Slezak-Prochazka ◽  
Patryk Bil ◽  
Joanna Rzeszowska-Wolny
Keyword(s):  
Target Genes ◽  
Redox Homeostasis ◽  
Messenger Rnas ◽  
Cellular Redox ◽  
Cell Responses ◽  
Regulatory Circuits ◽  
Micro Rnas ◽  
Cellular Behaviors ◽  
Homeostasis Regulation ◽  
Thioredoxin Reductases

In living cells Reactive Oxygen Species (ROS) participate in intra- and inter-cellular signaling and all cells contain specific systems that guard redox homeostasis. These systems contain both enzymes which may produce ROS such as NADPH-dependent and other oxidases or nitric oxide synthases, and ROS-neutralizing enzymes such as catalase, peroxiredoxins, thioredoxins, thioredoxin reductases, glutathione reductases, and many others. Most of the genes coding for these enzymes contain sequences targeted by micro RNAs (miRNAs), which are components of RNA-induced silencing complexes and play important roles in inhibiting translation of their targeted messenger RNAs (mRNAs). In this review we describe miRNAs that directly target and can influence enzymes responsible for scavenging of ROS and their possible role in cellular redox homeostasis. Regulation of antioxidant enzymes aims to adjust cells to survive in unstable oxidative environments; however, sometimes seemingly paradoxical phenomena appear where oxidative stress induces an increase in the levels of miRNAs which target genes which are supposed to neutralize ROS and therefore would be expected to decrease antioxidant levels. Here we show examples of such cellular behaviors and discuss the possible roles of miRNAs in redox regulatory circuits and further cell responses to stress.

scholarly journals REGULATORY MECHANISMS OF CELLULAR RESPIRATION

1950 ◽  
Vol 34 (2) ◽  
pp. 211-224 ◽  
Author(s):  
E. S. Guzman Barron ◽  
Maria Isabel Ardao ◽  
Marion Hearon
Keyword(s):  
Acetic Acid ◽  
Pyruvic Acid ◽  
No Oxidation ◽  
Yeast Cells ◽  
Acid Formation ◽  
Cellular Respiration ◽  
Acid Oxidase ◽  
Acid Solutions ◽  
Fluoroacetic Acid ◽  
A Cell

The rate of the aerobic metabolism of pyruvic acid by bakers' yeast cells is determined mainly by the amount of undissociated acid present. As a consequence, the greatest rate of oxidation was observed at pH 2.8. Oxidation, at a slow rate, started at pH 1.08; at pH 9.4 there was no oxidation at all. The anaerobic metabolism, only a fraction of the aerobic, was observed only in acid solutions. There was none at pH values higher than 3. Pyruvic acid in the presence of oxygen was oxidized directly to acetic acid; in the absence of oxygen it was metabolized mainly by dismutation to lactic and acetic acids, and CO2. Acetic acid formation was demonstrated on oxidation of pyruvic acid at pH 1.91, and on addition of fluoroacetic acid. Succinic acid formation was shown by addition of malonic acid. These metabolic pathways in a cell so rich in carboxylase may be explained by the arrangement of enzymes within the cell, so that carboxylase is at the center, while pyruvic acid oxidase is located at the periphery. Succinic and citric acids were oxidized only in acid solutions up to pH 4. Malic and α-ketoglutaric acids were not oxidized, undoubtedly because of lack of penetration.

Proteome and metabolome profiling of wild-type and YCA1 -knock-out yeast cells during acetic acid-induced programmed cell death

2015 ◽  
Vol 128 ◽  
pp. 173-188 ◽  
Author(s):  
Valentina Longo ◽  
Maša Ždralević ◽  
Nicoletta Guaragnella ◽  
Sergio Giannattasio ◽  
Lello Zolla ◽  
...  
Keyword(s):  
Cell Death ◽  
Acetic Acid ◽  
Programmed Cell Death ◽  
Yeast Cells ◽  
Wild Type ◽  
Knock Out ◽  
Metabolome Profiling

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

scholarly journals Gankyrin has an antioxidative role through the feedback regulation of Nrf2 in hepatocellular carcinoma

2016 ◽  
Vol 213 (5) ◽  
pp. 859-875 ◽  
Author(s):  
Chun Yang ◽  
Ye-xiong Tan ◽  
Guang-zhen Yang ◽  
Jian Zhang ◽  
Yu-fei Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Redox Homeostasis ◽  
Feedback Regulation ◽  
Cellular Redox ◽  
Intracellular Ros ◽  
Oxidative Stress Status ◽  
Kelch Domain ◽  
Cellular Stressors ◽  
Hcc Cells

Oxidative stress status has a key role in hepatocellular carcinoma (HCC) development and progression. Normally, reactive oxygen species (ROS) levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors. How HCC cells respond to excessive oxidative stress remains elusive. Here, we identified a feedback loop between gankyrin, an oncoprotein overexpressed in human HCC, and Nrf2 maintaining the homeostasis in HCC cells. Mechanistically, gankyrin was found to interact with the Kelch domain of Keap1 and effectively competed with Nrf2 for Keap1 binding. Increased expression of gankyrin in HCC cells blocked the binding between Nrf2 and Keap1, inhibiting the degradation of Nrf2 by proteasome. Interestingly, accumulation and translocation of Nrf2 increased the transcription of gankyrin through binding to the ARE elements in the promoter of gankyrin. The positive feedback regulation involving gankyrin and Nrf2 modulates a series of antioxidant enzymes, thereby lowering intracellular ROS and conferring a steadier intracellular environment, which prevents mitochondrial damage and cell death induced by excessive oxidative stress. Our results indicate that gankyrin is a regulator of cellular redox homeostasis and provide a link between oxidative stress and the development of HCC.

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