期刊
CELL REPORTS
卷 5, 期 3, 页码 781-790出版社
CELL PRESS
DOI: 10.1016/j.celrep.2013.09.043
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资金
- US-UK Fulbright Commission
- St. John's College, University of Cambridge
- National Institutes of Health (NIGMS)
- National Institutes of Health (NIA)
- National Institutes of Health (NINDS)
- Ellison Medical Foundation
- Daniel F. and Ada L. Rice Foundation
- Wellcome Trust
- UK Biotechnology and Biological Sciences Research Council
- Biotechnology and Biological Sciences Research Council [BB/H003843/1] Funding Source: researchfish
- BBSRC [BB/H003843/1] Funding Source: UKRI
The maintenance of protein solubility is a fundamental aspect of cellular homeostasis because protein aggregation is associated with a wide variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in living systems under stress or aging. A crucial question in this context is why only certain proteins appear to aggregate readily in vivo, whereas others do not. We identify here the proteins most vulnerable to aggregation as those whose cellular concentrations are high relative to their solubilities. We find that these supersaturated proteins represent a metastable subproteome involved in pathological aggregation during stress and aging and are over-represented in biochemical processes associated with neurodegenerative disorders. Consequently, such cellular processes become dysfunctional when the ability to keep intrinsically supersaturated proteins soluble is compromised. Thus, the simultaneous analysis of abundance and solubility can rationalize the diverse cellular pathologies linked to neurodegenerative diseases and aging.
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