Invited
Exploring protein redox switches in cells and aging

Why do we age? How do we cope with environmental and physical changes? What makes pathogens smarter than their host? One of the biological processes linking all these questions relates to the amazing ability of cells to respond to changes in the environment, such as changes in oxidant levels, and protect its proteome against damage. Here, I will cover different mechanisms and functions redox-regulated proteins play in stress-response mechanisms, including maintaining protein homeostasis during oxidative stress and aging. I will show how combination of structural mass spectrometry with computational modeling can advance our understanding in structural plasticity of redox-regulated proteins.

Moreover, I will discuss recently developed age-cutting technologies based on single cell analysis, redox cellular probes and mass spectrometry to monitor changes in cellular redox levels during chronological aging in yeast, and to dissect cell populations based on their redox status. Using this approach, we defined a redox-dependent heterogeneity of yeast cells and characterized growth, as well as proteomic and transcriptomic profiles of distinctive redox subpopulations. We report that, starting in late logarithmic growth, cells of the same age have a bi-modal distribution of oxidation status. A comparative proteomic analysis between these populations identified three key proteins, Hsp30, Dhh1, and Pnc1, which affect basal oxidation levels and may serve as first line of defense proteins in redox homeostasis.

References:

1. Radzinski et al., eLife 2018
2. Radzinski and D. Reichmann, Curr Genetics, 2018
3. Reichmann et al., Mol Cell, 2018
4. Rimon et al., Antioxid Redox Signal, 2017
5. Brandes et al., eLife, 2013
6. Reichmann et al., Cell, 2012