Cell biology and proposed mechanisms
Nrf2
Nrf2 (nuclear factor erythroid 2-related factor 2) is a protein that switches genes on. When a cell detects oxidative or chemical stress, Nrf2 moves into the cell nucleus and increases production of protective enzymes, including glutathione-making enzymes, superoxide dismutase and catalase.
Also called Nuclear factor erythroid 2-related factor 2, NFE2L2, KEAP1-NRF2 pathway
What it is
Nrf2 is a transcription factor: a protein whose job is to bind DNA and turn other genes on. In an unstressed cell it is held in the cytoplasm by a partner protein called KEAP1 and destroyed continuously, so very little of it accumulates. Oxidants and reactive chemicals modify sulphur-containing cysteine residues on KEAP1, the grip releases, and Nrf2 accumulates and enters the nucleus. There it binds stretches of DNA called antioxidant response elements and raises the output of a large battery of protective genes. The definitive account is The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis, Physiological Reviews (2018).
That much is settled biochemistry, and it is not specific to ozone, light or heat.
Why it comes up in ozone therapy
Nrf2 is the proposed link between a controlled oxidative challenge and a rise in the body’s own antioxidant defences. Sagai and Bocci set out the hypothesis in Medical Gas Research (2011): severe oxidative stress activates the inflammatory factor NF-κB, whereas moderate oxidative stress activates Nrf2 instead.
The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure, International Journal of Molecular Sciences (2019), reviews the supporting work, which is in cell culture and in animals given ozone by routes other than a sauna.
Why it matters here
Nrf2 is the molecule people reach for when explaining why a controlled dose of an oxidant might be good for you. It is a well-described pathway in cell biology, and the ozone side of it is still a proposal being researched.