Transient vitamin B5 starving improves mammalian cell homeostasis and protein production.

Details

Serval ID
serval:BIB_69D095209B51
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transient vitamin B5 starving improves mammalian cell homeostasis and protein production.
Journal
Metabolic engineering
Author(s)
Pourcel L., Buron F., Garcia F., Delaloix M.S., Le Fourn V., Girod P.A., Mermod N.
ISSN
1096-7184 (Electronic)
ISSN-L
1096-7176
Publication state
Published
Issued date
07/2020
Peer-reviewed
Oui
Volume
60
Pages
77-86
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Maintaining a metabolic steady state is essential for an organism's fitness and survival when confronted with environmental stress, and metabolic imbalance can be reversed by exposing the organism to fasting. Here, we attempted to apply this physiological principle to mammalian cell cultures to improve cellular fitness and consequently their ability to express recombinant proteins. We showed that transient vitamin B5 deprivation, an essential cofactor of central cellular metabolism, can quickly and irreversibly affect mammalian cell growth and division. A selection method was designed that relies on mammalian cell dependence on vitamin B5 for energy production, using the co-expression of the B5 transporter SLC5A6 and a gene of interest. We demonstrated that vitamin B5 selection persistently activates peroxisome proliferator-activated receptors (PPAR), a family of transcription factors involved in energy homeostasis, thereby altering lipid metabolism, improving cell fitness and therapeutic protein production. Thus, stable PPAR activation may constitute a cellular memory of past deprivation state, providing increased resistance to further potential fasting events. In other words, our results imply that cultured cells, once exposed to metabolic starvation, may display an improved metabolic fitness as compared to non-exposed cells, allowing increased resistance to cellular stress.
Keywords
Mammalian cells, Metabolic homeostasis, PPAR, SLC5A6 transporter, Vitamin B5
Pubmed
Web of science
Open Access
Yes
Create date
22/01/2021 10:42
Last modification date
02/02/2021 7:25
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