Oxygen deprivation and excess are both toxic. Thus, the body's ability to adapt to varying
oxygen tensions is critical for survival. While the
hypoxia transcriptional response has been well studied, the post-translational effects of
oxygen have been underexplored. In this study, we systematically investigate
protein turnover rates in mouse heart, lung, and brain under different inhaled
oxygen tensions. We find that the lung
proteome is the most responsive to varying
oxygen tensions. In particular, several extracellular matrix (ECM)
proteins are stabilized in the lung under both
hypoxia and
hyperoxia. Furthermore, we show that complex 1 of the electron transport chain is destabilized in
hyperoxia, in accordance with the exacerbation of associated disease models by
hyperoxia and rescue by
hypoxia. Moreover, we nominate MYBBP1A as a
hyperoxia transcriptional regulator, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of varying
oxygen tensions on
protein turnover rates and identifies tissue-specific mediators of
oxygen-dependent responses.