In Vivo Protein Turnover Rates in Varying Oxygen Tensions Nominate MYBBP1A as a Novel Mediator of the Hyperoxia Response

Oxygen deprivation and excess are both toxic to mammals. Thus, the body's ability to adapt to varying oxygen tensions is critical for survival. While the transcriptional response to acute hypoxia has been well-studied, the post-translational effects of hypoxia and hyperoxia 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 changes in oxygen tension, likely due to the direct exposure of alveoli to inhaled oxygen. In particular, several extracellular matrix (ECM) proteins such as collagens and laminins, are stabilized in the lung under both hypoxia and hyperoxia, suggesting their post-translational regulation. Furthermore, we validate our previous finding that complex 1 of the electron transport chain (ETC) is destabilized in hyperoxia, explaining the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a novel transcriptional regulator in hyperoxic lung, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of the effects of oxygen tensions on protein turnover rates and identifies novel tissue-specific mediators of oxygen-dependent responses. Overall design: The WT C57BL/6J mice were exposed to 21% or 80% oxygen for 5 days. Lung tissues were collected for 3' RNAseq (Quant-seq).