In accordance with their fundamental roles, chaperones are abundant proteins. Across species, they promote de novo protein folding and protein maturation 1, protein translocation 2, protein-complexes assembly and disassembly 3, protein disaggregation and refolding 4, and protein degradation 5. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.Ĭhaperones are highly conserved molecular machines that control cellular protein homeostasis (proteostasis). Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. Together with variable chaperones, they form tissue-specific functional networks. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. Yet, the organization of the chaperone system across physiological human tissues has received little attention. The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific.

Chaperone meaning