| 1. |
- Bodvard, Kristofer, 1981, et al.
(författare)
-
Light-sensing via hydrogen peroxide and a peroxiredoxin
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Yeast lacks dedicated photoreceptors; however, blue light still causes pronounced oscillations of the transcription factor Msn2 into and out of the nucleus. Here we show that this poorly understood phenomenon is initiated by a peroxisomal oxidase, which converts light into a hydrogen peroxide (H2O2) signal that is sensed by the peroxiredoxin Tsa1 and transduced to thioredoxin, to counteract PKA-dependent Msn2 phosphorylation. Upon H2O2, the nuclear retention of PKA catalytic subunits, which contributes to delayed Msn2 nuclear concentration, is antagonized in a Tsa1-dependent manner. Conversely, peroxiredoxin hyperoxidation interrupts the H2O2 signal and drives Msn2 oscillations by superimposing on PKA feedback regulation. Our data identify a mechanism by which light could be sensed in all cells lacking dedicated photoreceptors. In particular, the use of H2O2 as a second messenger in signalling is common to Msn2 oscillations and to light-induced entrainment of circadian rhythms and suggests conserved roles for peroxiredoxins in endogenous rhythms.
|
|
| 2. |
|
|
| 3. |
- Hanzén, Sarah, et al.
(författare)
-
Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
- 2016
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 166:1, s. 140-151
-
Tidskriftsartikel (refereegranskat)abstract
- Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.
|
|
| 4. |
- Molin, Mikael, 1973, et al.
(författare)
-
Protein kinase A controls yeast growth in visible light
- 2020
-
Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
|
|
| 5. |
- Roger, Friederike, et al.
(författare)
-
Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
- 2020
-
Ingår i: eLife. - 2050-084X. ; 9, s. 1-32
-
Tidskriftsartikel (refereegranskat)abstract
- Peroxiredoxins are H2O2 scavenging enzymes that also carry out H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2 and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H2O2, but by repressing the nutrient signaling Ras-cAMP-PKA pathway at the level of the protein kinase A (PKA) enzyme. Tsa1 stimulates sulfenylation of cysteines in the PKA catalytic subunit by H2O2 and a significant proportion of the catalytic subunits are glutathionylated on two cysteine residues. Redox modification of the conserved Cys243 inhibits the phosphorylation of a conserved Thr241 in the kinase activation loop and enzyme activity, and preventing Thr241 phosphorylation can overcome the H2O2 sensitivity of Tsa1-deficient cells. Results support a model of aging where nutrient signaling pathways constitute hubs integrating information from multiple aging-related conduits, including a peroxiredoxin-dependent response to H2O2.
|
|
| 6. |
- Roger, Friederike
(författare)
-
Peroxiredoxins in Redox Signaling and Aging
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peroxiredoxins have emerged as conserved modulators of the rate of aging in yeast and multicellular organisms and play a role in lifespan extension through the anti-aging intervention caloric restriction. Yet, it is not clear through what mechanism peroxiredoxins extend lifespan. First discovered as hydrogen peroxide scavengers, peroxiredoxins have been shown to have a genome protective function, to act as chaperones, to play a role in circadian rhythms and to be involved in redox signaling. In this thesis, I tried to identify the underlying mechanisms for peroxiredoxin mediated lifespan extension and its role in redox signaling. Using the yeast Saccharomyces cerevisiae as a model organism, we could show that the lifespan extension by the peroxiredoxin Tsa1 is not linked to increased genome stability. Our data indicates that Tsa1 recruits molecular chaperones to protein aggregates formed during oxidative stress and reduces the number of protein aggregates that accumulate during aging. Surprisingly, this contributes just to a limited extend to lifespan extension, as a mutant not able to form a chaperone still has a normal lifespan. Instead, redox-signaling that reduces protein kinase A (PKA) activity through Tsa1 mediated oxidation seems to be preeminently responsible for lifespan extension. Interestingly, the same signaling pathway is used in yeast to react to light stress. Hydrogen peroxide formed upon illumination by a conserved peroxisomal oxidase leads to increased redox cycling of Tsa1. Tsa1 then reduces PKA activity allowing the subsequent nuclear localization of the transcription factors Msn2 and Msn4 that induce transcription of stress related genes. Our data thus clarify an important aspect of the role of peroxiredoxins in circadian rhythms, namely they mediate an organismal light response.
|
|
| 7. |
- Stough, Roger, et al.
(författare)
-
Family business and regional science: "Bridging the gap"
- 2015
-
Ingår i: The Journal of Family Business Strategy. - : ELSEVIER SCIENCE BV. - 1877-8585 .- 1877-8593. ; 6:4, s. 208-218
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this special issue is to stimulate research on the interaction between the fields of family business and regional science. Despite their overlapping themes and the high relevance of family firms for many regions, the two academic fields have emerged independently from each other, and little exchange exists. We discuss not only the role family firms play within the region in order to enhance our understanding of the ways family firms may (or may not) contribute to regional economic development but also the effect of socio-spatial and institutional context on firm behavior and performance. The set of empirical and theoretical articles included in this special issue represents an important early step bridging insights between the two fields. (C) 2015 Published by Elsevier Ltd.
|
|
