Quantitative Proteomics of Sleep-Deprived Mouse Brains Reveals Global Changes in Mitochondrial Proteins.
Sleep is a ubiquitous, tightly regulated, and evolutionarily conserved behavior observed in almost all animals. Prolonged sleep deprivation can be fatal, indicating that sleep is a physiological necessity. However, little is known about its core function. To gain insight into this mystery, we used advanced quantitative proteomics technology to survey the global changes in brain protein abundance. Aiming to gain a comprehensive profile, our proteomics workflow included filter-aided sample preparation (FASP), which increased the coverage of membrane proteins; tandem mass tag (TMT) labeling, for relative quantitation; and high resolution, high mass accuracy, high throughput mass spectrometry (MS). In total, we obtained the relative abundance ratios of 9888 proteins encoded by 6070 genes. Interestingly, we observed significant enrichment for mitochondrial proteins among the differentially expressed proteins. This finding suggests that sleep deprivation strongly affects signaling pathways that govern either energy metabolism or responses to mitochondrial stress. Additionally, the differentially-expressed proteins are enriched in pathways implicated in age-dependent neurodegenerative diseases, including Parkinson's, Huntington's, and Alzheimer's, hinting at possible connections between sleep loss, mitochondrial stress, and neurodegeneration.
National Institute of Biological Sciences, Beijing, China.
Jing
http://orcid.org/0000-0002-6665-7457
J
Ren
National Institute of Biological Sciences, Beijing, China.
Mei-Jun
MJ
Zhang
National Institute of Biological Sciences, Beijing, China.
Tie-Mei
TM
Li
National Institute of Biological Sciences, Beijing, China.
Ju-En
JE
Zhang
National Institute of Biological Sciences, Beijing, China.
Rui
R
Lin
National Institute of Biological Sciences, Beijing, China.
She
S
Chen
National Institute of Biological Sciences, Beijing, China.
Minmin
M
Luo
National Institute of Biological Sciences, Beijing, China.
Meng-Qiu
MQ
Dong
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