Analysis of proteome dynamics in the mouse brain

Area of Science:

• Systems Biology
• Proteomics
• Metabolic Regulation

Background:

• Global mRNA and protein expression analyses are advanced.
• Large-scale in vivo studies of protein dynamics and turnover are lacking.
• Protein turnover is crucial for proteome homeostasis and impacts physiological/pathological processes.

Purpose of the Study:

• To conduct the most comprehensive in vivo analysis of mammalian proteome turnover.
• To measure protein turnover rates across multiple mouse tissues.
• To compare protein turnover dynamics between different tissues and within cellular components.

Main Methods:

• Organism-wide isotopic labeling in mice.
• Quantification of turnover rates for approximately 2,500 proteins.
• Comparative analysis of protein turnover in brain, liver, and blood tissues.

Main Results:

• Protein turnover rates spanned four orders of magnitude.
• Proteins with similar functions within tissues exhibited similar turnover rates.
• Brain proteins showed significantly slower turnover (9.0 d) compared to liver (3.0 d) and blood (3.5 d).
• Mitochondrial proteins displayed synchronized turnover.
• Subunits within well-defined protein complexes turned over coordinately.

Conclusions:

• This study provides the most comprehensive in vivo dataset on mammalian proteome turnover.
• Tissue-specific differences in protein turnover exist, with the brain being notably slower.
• The developed methodology is adaptable for assessing proteome homeostasis in various model organisms.
• This approach may be valuable for studying neurodegenerative diseases.