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Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster.

Menger KE, James AM, Cochemé HM, Harbour ME, Chouchani ET, Ding S, Fearnley IM, Partridge L, Murphy MP - Cell Rep (2015)

Bottom Line: Surprisingly, these cysteine residues did not become more oxidized with age.In contrast, 24 hr of fasting dramatically oxidized cysteine residues that were reduced under fed conditions while also reducing cysteine residues that were initially oxidized.We conclude that fasting, but not aging, dramatically alters cysteine-residue redox status in D. melanogaster.

View Article: PubMed Central - PubMed

Affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK; Institute of Ophthalmology, University College London, London EC1V 9EL, UK.

No MeSH data available.


Related in: MedlinePlus

Reversible Oxidation Levels of Cysteine Residues in Aging D. melanogaster(A) Lifespan of control female flies. Cohorts of flies were taken to analyze protein cysteine residue redox state of young (7 days), middle-aged (28 days), and old (56 days) flies.(B) Distribution of cysteine peptides plotted against their redox states for 7-, 28-, and 56-day-old control flies. Data are means ± SEM. The red curve is for 7-day-old control flies.(C) Oxidation state of cysteine residues present in 56-day-old flies plotted against 7-day-old flies. The dotted line slope = 1, while the continuous line is the least-squares best-fit line to the data. Data from 263 unique peptides identified at least three times under both conditions are plotted. Red symbols (n = 6) indicate low-stringency significance with p < 0.05 assessed by a non-paired, two-tailed Student’s t test.See also Figure S3.
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fig3: Reversible Oxidation Levels of Cysteine Residues in Aging D. melanogaster(A) Lifespan of control female flies. Cohorts of flies were taken to analyze protein cysteine residue redox state of young (7 days), middle-aged (28 days), and old (56 days) flies.(B) Distribution of cysteine peptides plotted against their redox states for 7-, 28-, and 56-day-old control flies. Data are means ± SEM. The red curve is for 7-day-old control flies.(C) Oxidation state of cysteine residues present in 56-day-old flies plotted against 7-day-old flies. The dotted line slope = 1, while the continuous line is the least-squares best-fit line to the data. Data from 263 unique peptides identified at least three times under both conditions are plotted. Red symbols (n = 6) indicate low-stringency significance with p < 0.05 assessed by a non-paired, two-tailed Student’s t test.See also Figure S3.

Mentions: H2O2 is a key mediator of thiol redox state that increases with age in flies (Cochemé et al., 2011). Aging has also been correlated with an increase in oxidative damage in flies (Jacobson et al., 2010), and protein thiols become oxidized upon chronological aging in yeast (Magherini et al., 2009). We used OxICAT to quantify the effect of aging on the oxidation of cysteine residues (Figure 3A). Surprisingly, despite increases in H2O2 (Cochemé et al., 2011) and oxidative damage with age, the cysteine-residue oxidation state did not shift between young (7 days), middle-aged (28 days), and old (56 days) control flies, and the weighted mean percentage oxidation was also almost unaffected (Figure 3B). To see if there were shifts in the redox state of individual proteins with age that were masked by the overall trend, we plotted the redox state of individual cysteine residues detected in both the young and old control flies and again observed no change in redox state (Figure 3C). Similarly, there were no changes between 7 days and 28 days (Figure S3A) or between 28 days and 56 days (Figure S3B; Table S3).


Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster.

Menger KE, James AM, Cochemé HM, Harbour ME, Chouchani ET, Ding S, Fearnley IM, Partridge L, Murphy MP - Cell Rep (2015)

Reversible Oxidation Levels of Cysteine Residues in Aging D. melanogaster(A) Lifespan of control female flies. Cohorts of flies were taken to analyze protein cysteine residue redox state of young (7 days), middle-aged (28 days), and old (56 days) flies.(B) Distribution of cysteine peptides plotted against their redox states for 7-, 28-, and 56-day-old control flies. Data are means ± SEM. The red curve is for 7-day-old control flies.(C) Oxidation state of cysteine residues present in 56-day-old flies plotted against 7-day-old flies. The dotted line slope = 1, while the continuous line is the least-squares best-fit line to the data. Data from 263 unique peptides identified at least three times under both conditions are plotted. Red symbols (n = 6) indicate low-stringency significance with p < 0.05 assessed by a non-paired, two-tailed Student’s t test.See also Figure S3.
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Related In: Results  -  Collection

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fig3: Reversible Oxidation Levels of Cysteine Residues in Aging D. melanogaster(A) Lifespan of control female flies. Cohorts of flies were taken to analyze protein cysteine residue redox state of young (7 days), middle-aged (28 days), and old (56 days) flies.(B) Distribution of cysteine peptides plotted against their redox states for 7-, 28-, and 56-day-old control flies. Data are means ± SEM. The red curve is for 7-day-old control flies.(C) Oxidation state of cysteine residues present in 56-day-old flies plotted against 7-day-old flies. The dotted line slope = 1, while the continuous line is the least-squares best-fit line to the data. Data from 263 unique peptides identified at least three times under both conditions are plotted. Red symbols (n = 6) indicate low-stringency significance with p < 0.05 assessed by a non-paired, two-tailed Student’s t test.See also Figure S3.
Mentions: H2O2 is a key mediator of thiol redox state that increases with age in flies (Cochemé et al., 2011). Aging has also been correlated with an increase in oxidative damage in flies (Jacobson et al., 2010), and protein thiols become oxidized upon chronological aging in yeast (Magherini et al., 2009). We used OxICAT to quantify the effect of aging on the oxidation of cysteine residues (Figure 3A). Surprisingly, despite increases in H2O2 (Cochemé et al., 2011) and oxidative damage with age, the cysteine-residue oxidation state did not shift between young (7 days), middle-aged (28 days), and old (56 days) control flies, and the weighted mean percentage oxidation was also almost unaffected (Figure 3B). To see if there were shifts in the redox state of individual proteins with age that were masked by the overall trend, we plotted the redox state of individual cysteine residues detected in both the young and old control flies and again observed no change in redox state (Figure 3C). Similarly, there were no changes between 7 days and 28 days (Figure S3A) or between 28 days and 56 days (Figure S3B; Table S3).

Bottom Line: Surprisingly, these cysteine residues did not become more oxidized with age.In contrast, 24 hr of fasting dramatically oxidized cysteine residues that were reduced under fed conditions while also reducing cysteine residues that were initially oxidized.We conclude that fasting, but not aging, dramatically alters cysteine-residue redox status in D. melanogaster.

View Article: PubMed Central - PubMed

Affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK; Institute of Ophthalmology, University College London, London EC1V 9EL, UK.

No MeSH data available.


Related in: MedlinePlus