Jun 24, 2022
News
Invited speaker seminar
Bruce Morgan, PhD
Bruce is Professor for Biochemistry at the Faculty of Natural Sciences and Technology of the Universität des Saarlandes. It talk is titled
Cellular redox cycles: Fundamental regulators of biological timing and cell division
Friday, 24 June | 11:00 AM | hosted by Ünal Coskun | B CUBE seminar rooms B/C (E73/E74)
Abstract
Redox and metabolic cycles have been reported in ultradian, circadian and cell cycle-synchronized systems. Redox cycles can persist in the absence of transcription and cyclin-CDK activity, indicating that cells contain multiple coupled oscillators. Nonetheless, the causal relationships and molecular mechanisms by which redox cycles are embedded within ultradian, circadian or cell division cycles remain largely elusive.
The budding yeast, Saccharomyces cerevsiae, harbors an ultradian oscillator, the yeast metabolic cycle (YMC), which comprises metabolic/redox cycles, transcriptional cycles and synchronized cell division. Using novel ultra-sensitive, genetically encoded fluorescent
reporters, we reveal the existence of robust cycling of H2O2 and peroxiredoxin oxidation during the YMC and show that peroxiredoxin inactivation disrupts metabolic cycling and abolishes coupling with cell division. We find that thiol-disulfide oxidants and reductants
predictably modulate the switching between different YMC metabolic states, which in turn predictably perturbs cell cycle entry and exit. We propose that oscillatory H2O2 -dependent protein thiol oxidation is a key regulator of metabolic cycling and its coordination with cell division.
5 most important publications
1.Amponsah PS, …, Morgan B. (2021) Peroxiredoxins couple metabolism and cell division in an ultradian cycle. Nature Chem. Biol. 17(4):477-484.
2.Zimmermann J, …, Morgan B. One cysteine is enough: A monothiol Grx can functionally replace all cytosolic Trx and dithiol Grx. Redox Biol. 2020. 36:101598.
3.Liedgens L, …, Gohlke H*, Morgan B*, and Deponte M*. (2020) Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins. Nature Commun. 11:1725. *Corresponding authors
4.Morgan B*, …, Dick TP*. Real-time monitoring of basal H2O2 levels with peroxiredoxin-based probes. Nat Chem Biol. 2016 Jun;12(6):437-4. Epub 2016 Apr 18. *Corresponding authors
5.Morgan B, …, Dick TP. Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis. Nat Chem Biol. 2013 Feb;9(2):119-25.