L-13 - Redox regulation under physiological oxygen levels

The extensive oxygen gradient between the air we breathe (PO2 ~21 kPa) and its distribution within mitochondria (as low as ~0.5–1 kPa) is testament to the efforts expended in limiting its inherent toxicity. It has long been recognised that cell culture undertaken under room air conditions falls short of replicating this protection in vitro. Despite this, difficulty in accurately determining the appropriate O2 level(s) in which to culture cells, coupled with a lack of the technology to replicate and maintain a physiological O2 environment in vitro, has hindered addressing this issue. This lecture will review our current understanding of tissue PO2 distribution in vivo, and summarize the attempts made to replicate these conditions in vitro. State-of-the-art techniques employed to accurately determine O2 levels, as well as the issues associated with reproducing physiological O2 levels in vitro will provide the framework for researchers to undertake cell culture under O2 levels relevant to specific tissues and organs. We aim to facilitate a paradigm shift, enabling translation of findings under physiological conditions in vitro to disease pathology and the design of novel therapeutics.