Periodic Reporting for period 3 - Redox Relays (Detecting, understanding and exploiting intracellular redox signaling relays)
Periodo di rendicontazione: 2020-10-01 al 2022-03-31
In all forms of life, metabolism fundamentally depends on redox (reduction-oxidation) reactions, i.e. chemical transformations in which electrons are transferred between molecules. For example, photosynthesis, respiration and fermentation all depend on the reshuffling of electrons between donors (reductants) and recipients (oxidants). Organisms and their cells need to constantly adapt to changes in metabolism, as for example caused by variations in the availability of oxidants (e.g. oxygen) and reductants (e.g. sugars). It is now recognized that many, if not most, proteins, the executioners of almost all cell functions, can ‘feel’ the presence of key redox molecules (oxidants and reductants), to change their activity in an adaptive manner, so that cellular behavior (e.g. growth) matches metabolically imposed opportunities or restrictions. However, it has been difficult to explain how proteins are specifically regulated by redox reactions, at the right time and place inside the cell, a process called ‘redox regulation’ or ‘redox signaling’. The emerging solution to this conundrum is that oxidants and reductants are often channeled towards target proteins through protein-protein relay chains which assemble and act in a highly specific and localized manner. This project aims to systematically uncover, monitor and manipulate the redox relay chains that give specificity and efficiency to redox signaling.
To this end, all proteins in a cell have been individually tagged with biosensors that allow to monitor their immediate redox environment. During the first half of the project, the approach identified tiny dynamic ‘islands of oxidation’, most prominently in the nucleus, the control center of the cell. These ‘islands’ appear to be centered around protein complexes involved in gene regulation. It seems that gene expression is regulated by highly localized redox events that depend on metabolic conditions.
We expect to document this phenomenon in further detail and map out specific examples until the end of the project.