Journal article
The stress of protein misfolding: from single cells to multicellular organisms
Cold Spring Harbor perspectives in biology, Vol.3(6), pp.1-18
06/01/2011
DOI: 10.1101/cshperspect.a009704
PMCID: PMC3098679
PMID: 21536706
Abstract
Organisms survive changes in the environment by altering their rates of metabolism, growth, and reproduction. At the same time, the system must ensure the stability and functionality of its macromolecules. Fluctuations in the environment are sensed by highly conserved stress responses and homeostatic mechanisms, and of these, the heat shock response (HSR) represents an essential response to acute and chronic proteotoxic damage. However, unlike the strategies employed to maintain the integrity of the genome, protection of the proteome must be tailored to accommodate the normal flux of nonnative proteins and the differences in protein composition between cells, and among individuals. Moreover, adult cells are likely to have significant differences in the rates of synthesis and clearance that are influenced by intrinsic errors in protein expression, genetic polymorphisms, and fluctuations in physiological and environmental conditions. Here, we will address how protein homeostasis (proteostasis) is achieved at the level of the cell and organism, and how the threshold of the stress response is set to detect and combat protein misfolding. For metazoans, the requirement for coordinated function and growth imposes additional constraints on the detection, signaling, and response to misfolding, and requires that the HSR is integrated into various aspects of organismal physiology, such as lifespan. This is achieved by hierarchical regulation of heat shock factor 1 (HSF1) by the metabolic state of the cell and centralized neuronal control that could allow optimal resource allocation between cells and tissues. We will examine how protein folding quality control mechanisms in individual cells may be integrated into a multicellular level of control, and further, even custom-designed to support individual variability and impose additional constraints on evolutionary adaptation.
Details
- Title: Subtitle
- The stress of protein misfolding: from single cells to multicellular organisms
- Creators
- Tali Gidalevitz - Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USAVeena PrahladRichard I Morimoto
- Resource Type
- Journal article
- Publication Details
- Cold Spring Harbor perspectives in biology, Vol.3(6), pp.1-18
- Publisher
- United States
- DOI
- 10.1101/cshperspect.a009704
- PMID
- 21536706
- PMCID
- PMC3098679
- ISSN
- 1943-0264
- eISSN
- 1943-0264
- Grant note
- AG026647 / NIA NIH HHS R01 AG026647 / NIA NIH HHS NS047331 / NINDS NIH HHS R37 AG026647 / NIA NIH HHS R01 GM038109 / NIGMS NIH HHS R01 NS047331 / NINDS NIH HHS R37 GM038109 / NIGMS NIH HHS GM081192 / NIGMS NIH HHS GM038109 / NIGMS NIH HHS
- Language
- English
- Date published
- 06/01/2011
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983991999802771
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