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

Détails

Ressource 1Télécharger: Pourcel et al 2020.pdf (1921.24 [Ko])
Etat: Public
Version: de l'auteur
Licence: CC BY 4.0
ID Serval
serval:BIB_A31339F7E913
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Transient vitamin B5 starving improves mammalian cell homeostasis and protein production.
Périodique
Metabolic engineering
Auteur(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
Statut éditorial
Publié
Date de publication
07/2020
Peer-reviewed
Oui
Volume
60
Pages
77-86
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Mammalian cells, Metabolic homeostasis, PPAR, SLC5A6 transporter, Vitamin B5
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/07/2020 11:12
Dernière modification de la notice
14/07/2021 7:11
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