Abstract
The proteostasis network (PN) regulates protein synthesis, folding, transport, and degradation to maintain proteome integrity and limit the accumulation of protein aggregates, a hallmark of aging and degenerative diseases. In multicellular organisms, the PN is regulated at the cellular, tissue, and systemic level to ensure organismal health and longevity. Here we review these three layers of PN regulation and examine how they collectively maintain cellular homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis across tissues. A precise understanding of these layers of control has important implications for organismal health and could offer new therapeutic approaches for neurodegenerative diseases and other chronic disorders related to PN dysfunction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1231-1241 |
| Number of pages | 11 |
| Journal | Journal of Cell Biology |
| Volume | 216 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2017 |
Funding
We thank the members of the Morimoto laboratory for valuable input during the preparation of this work, particularly Thomas Stoeger for helpful discussions and advice on the data analysis. We also thank Patricija van Oosten-Hawle, Johnathan Labbadia, and Jian Li for critical reading of the manuscript. This study was supported by grants from the National Institutes of Health (National Institute on Aging [grants R37 AG026647 and AG049665] and National Institute of Mental Health), the Ellison Medical Foundation, the Glenn Family Foundation, the Chicago Biomedical Consortium, and the Daniel F. and Ada L. Rice Foundation to R.I. Morimoto and a postdoctoral fellowship from the National Ataxia Foundation to L.C. Bott.
ASJC Scopus subject areas
- Cell Biology