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Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan

Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show tha...

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Main Authors: Noormohammadi, Alireza (Author) , Khodakarami, Amirabbas (Author) , Gutierrez-Garcia, Ricardo (Author) , Lee, Hyun Ju (Author) , Koyuncu, Seda (Author) , König, Tim (Author) , Schindler, Christina (Author) , Saez, Isabel (Author) , Fatima, Azra (Author) , Dieterich, Christoph (Author) , Vilchez, David (Author)
Format: Article (Journal)
Language:English
Published: 28 Nov 2016
In: Nature Communications
Year: 2016, Volume: 7, Pages: 13649
ISSN:2041-1723
DOI:10.1038/ncomms13649
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms13649
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms13649
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Author Notes:Alireza Noormohammadi, Amirabbas Khodakarami, Ricardo Gutierrez-Garcia, Hyun Ju Lee, Seda Koyuncu, Tim König, Christina Schindler, Isabel Saez, Azra Fatima, Christoph Dieterich & David Vilchez
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Summary:Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation of mutant Huntingtin protein. We further show that increased expression of CCT8 in somatic tissues extends Caenorhabditis elegans lifespan in a TRiC/CCT-dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington’s disease. Our results suggest proteostasis is a common principle that links organismal longevity with hESC immortality.
Item Description:Gesehen am 26.06.2020
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms13649

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