In vivo protein turnover rates in varying oxygen tensions nominate MYBBP1A as a mediator of the hyperoxia response

Xuewen Chen; Augustinus G Haribowo; Alan H Baik; Andrea Fossati; Erica Stevenson; Yiwen R Chen; Nabora S Reyes; Tien Peng; Michael A Matthay; Michela Traglia; Alexander R Pico; Daniel F Jarosz; Abigail Buchwalter; Sina Ghaemmaghami; Danielle L Swaney; Isha H Jain

doi:10.1126/sciadv.adj4884

In vivo protein turnover rates in varying oxygen tensions nominate MYBBP1A as a mediator of the hyperoxia response

Sci Adv. 2023 Dec 8;9(49):eadj4884. doi: 10.1126/sciadv.adj4884. Epub 2023 Dec 8.

Authors

Xuewen Chen^{1

2

3}, Augustinus G Haribowo^{1

2}, Alan H Baik^{1

4}, Andrea Fossati^{1

5

6}, Erica Stevenson^{1

5

6}, Yiwen R Chen⁷, Nabora S Reyes⁸, Tien Peng^{8

9}, Michael A Matthay^{10

11}, Michela Traglia¹², Alexander R Pico¹², Daniel F Jarosz^{7

13}, Abigail Buchwalter^{10

14

15}, Sina Ghaemmaghami^{16

17}, Danielle L Swaney^{1

5

6}, Isha H Jain^{1

2

9

10}

Affiliations

¹ Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
² Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
³ Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA.
⁴ Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA, USA.
⁵ Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
⁶ Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
⁷ Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
⁸ Department of Medicine and Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
⁹ Bakar Aging Research Institute, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
¹¹ Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA, USA.
¹² Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA.
¹³ Department of Developmental Biology, Stanford University, CA, USA.
¹⁴ Department of Physiology, University of California San Francisco, San Francisco, CA, USA.
¹⁵ Chan Zuckerberg Biohub, San Francisco, CA, USA.
¹⁶ Mass Spectrometry Resource Laboratory, University of Rochester, Rochester, NY, USA.
¹⁷ Department of Biology, University of Rochester, Rochester, NY, USA.

Abstract

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.

MeSH terms

Animals
Brain / metabolism
Hyperoxia* / genetics
Hyperoxia* / metabolism
Hypoxia / metabolism
Lung / metabolism
Mice
Oxygen* / metabolism

Substances

Oxygen
Mybbp1a protein, mouse

Abstract

MeSH terms

Substances

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