Oxidative Stress Promotes Specific Protein Damage inSaccharomyces cerevisiae

Cabiscol, Elisa; Piulats, Eva; Echave, Pedro; Herrero, Enrique; Ros, Joaquim

doi:10.1016/s0021-9258(19)61523-1

Cited by 324 publications

(19 citation statements)

References 44 publications

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“…5A). We then assayed oxidative damage to proteins through the use of 2,4-dinitrophenylhydrazine, a compound that reacts with carbonyl groups of proteins (14). Carbonyl groups are common by-products of oxidative damage to amino acid side chains.…”

Section: Overexpression Of Mitochondrial Iron Transporters Protects ⌬Ccc1 Cells From Iron Toxicity By Lowering Cytosolic Iron-to Examine mentioning

confidence: 99%

Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

Lin

Jia

et al. 2011

Journal of Biological Chemistry

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Iron storage in yeast requires the activity of the vacuolar iron transporter Ccc1. Yeast with an intact CCC1 are resistant to iron toxicity, but deletion of CCC1 renders yeast susceptible to iron toxicity. We used genetic and biochemical analysis to identify suppressors of high iron toxicity in Δccc1 cells to probe the mechanism of high iron toxicity. All genes identified as suppressors of high iron toxicity in aerobically grown Δccc1 cells encode organelle iron transporters including mitochondrial iron transporters MRS3, MRS4, and RIM2. Overexpression of MRS3 suppressed high iron toxicity by decreasing cytosolic iron through mitochondrial iron accumulation. Under anaerobic conditions, Δccc1 cells were still sensitive to high iron toxicity, but overexpression of MRS3 did not suppress iron toxicity and did not result in mitochondrial iron accumulation. We conclude that Mrs3/Mrs4 can sequester iron within mitochondria under aerobic conditions but not anaerobic conditions. We show that iron toxicity in Δccc1 cells occurred under both aerobic and anaerobic conditions. Microarray analysis showed no evidence of oxidative damage under anaerobic conditions, suggesting that iron toxicity may not be solely due to oxidative damage. Deletion of TSA1, which encodes a peroxiredoxin, exacerbated iron toxicity in Δccc1 cells under both aerobic and anaerobic conditions, suggesting a unique role for Tsa1 in iron toxicity.

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Section: Overexpression Of Mitochondrial Iron Transporters Protects ⌬Ccc1 Cells From Iron Toxicity By Lowering Cytosolic Iron-to Examine mentioning

confidence: 99%

Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

Lin

Jia

et al. 2011

Journal of Biological Chemistry

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“…In yeast, a driving mechanism for the growing damage burden is the asymmetric distribution of damaged components between mother and daughter cell [8,9]. An important precursor of protein damage is oxidative stress that is shown to increase with age [10][11][12] and is a byproduct of metabolic activity in the cells' mitochondria [12][13][14][15]. Reactive oxygen and nitrogen species 1 (ROS/RNS) are one of the most well-studied byproducts to which cells are constantly exposed even under normal conditions [16,17].…”

Section: Introductionmentioning

confidence: 99%

Multi-scale model suggests the trade-off between protein and ATP demand as a driver of metabolic changes during yeast replicative ageing

Schnitzer

Österberg

Skopa

et al. 2022

Preprint

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The accumulation of protein damage is one of the major drivers of replicative ageing, describing a cell’s reduced ability to reproduce over time even under optimal conditions. Reactive oxygen and nitrogen species are precursors of protein damage and therefore tightly linked to ageing. At the same time, they are an inevitable by-product of the cell’s metabolism. Cells are able to sense high levels of reactive oxygen and nitrogen species and can subsequently adapt their metabolism through gene regulation to slow down damage accumulation. However, the older or damaged a cell is the less flexibility it has to allocate enzymes across the metabolic network, forcing further adaptions in the metabolism. To investigate changes in the metabolism during replicative ageing, we developed an multi-scale mathematical model using budding yeast as a model organism. The model consists of three interconnected modules: a Boolean model of the signalling network, an enzyme-constrained flux balance model of the central carbon metabolism and a dynamic model of growth and protein damage accumulation with discrete cell divisions. The model can explain known features of replicative ageing, like average lifespan and increase in generation time during successive division, in yeast wildtype cells by a decreasing pool of functional enzymes and an increasing energy demand for maintenance. We further used the model to identify three consecutive metabolic phases, that a cell can undergo during its life, and their influence on the replicative potential, and proposed an intervention span for lifespan control.

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“…Although this possibility cannot be completely ruled out, it seems unlikely. Thus, Cabiscol and coworkers found that the levels of protein carbonyl content, an indicator of oxidative damage, in crude extracts of yeast cells grown in YPG (glycerol as carbon source) were 1.6 times higher than those in cells grown in YPD (glucose as carbon source) [184]. Nevertheless, we must bear in mind that different methods of estimating ROS levels can yield different results.…”

Section: Institutional Review Board Statement: Not Applicablementioning

confidence: 99%

The Role of Methionine Residues in the Regulation of Liquid-Liquid Phase Separation

Aledo

2021

Biomolecules

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Membraneless organelles are non-stoichiometric supramolecular structures in the micron scale. These structures can be quickly assembled/disassembled in a regulated fashion in response to specific stimuli. Membraneless organelles contribute to the spatiotemporal compartmentalization of the cell, and they are involved in diverse cellular processes often, but not exclusively, related to RNA metabolism. Liquid-liquid phase separation, a reversible event involving demixing into two distinct liquid phases, provides a physical framework to gain insights concerning the molecular forces underlying the process and how they can be tuned according to the cellular needs. Proteins able to undergo phase separation usually present a modular architecture, which favors a multivalency-driven demixing. We discuss the role of low complexity regions in establishing networks of intra- and intermolecular interactions that collectively control the phase regime. Post-translational modifications of the residues present in these domains provide a convenient strategy to reshape the residue–residue interaction networks that determine the dynamics of phase separation. Focus will be placed on those proteins with low complexity domains exhibiting a biased composition towards the amino acid methionine and the prominent role that reversible methionine sulfoxidation plays in the assembly/disassembly of biomolecular condensates.

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Oxidative Stress Promotes Specific Protein Damage inSaccharomyces cerevisiae

Cited by 324 publications

References 44 publications

Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

Multi-scale model suggests the trade-off between protein and ATP demand as a driver of metabolic changes during yeast replicative ageing

The Role of Methionine Residues in the Regulation of Liquid-Liquid Phase Separation

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