Peroxiredoxins couple metabolism and cell division in an ultradian cycle

Redox cycles have been reported in ultradian, circadian and cell cycle-synchronized systems. Redox cycles persist in the absence of transcription and cyclin-CDK activity, indicating that cells harbor 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. Yeast harbor an ultradian oscillator, the yeast metabolic cycle (YMC), which comprises metabolic/redox cycles, transcriptional cycles and synchronized cell division. Here, 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.

Automated summary

Redox cycles play a crucial role in regulating metabolic and cell division cycles within cells, with oscillatory H2O2-dependent protein thiol oxidation serving as a key regulator. The cycling of H2O2 and peroxiredoxin oxidation during the YMC is essential for maintaining metabolic cycling and coupling it with cell division. Thiol-disulfide oxidants and reductants predictably modulate the switching between different metabolic states in the YMC, ultimately affecting cell cycle progression.