Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 02 2022
10 02 2022
Historique:
received:
28
06
2021
accepted:
27
01
2022
entrez:
11
2
2022
pubmed:
12
2
2022
medline:
4
3
2022
Statut:
epublish
Résumé
When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation-known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.
Identifiants
pubmed: 35145105
doi: 10.1038/s41467-022-28467-6
pii: 10.1038/s41467-022-28467-6
pmc: PMC8831649
doi:
Substances chimiques
Proteome
0
Saccharomyces cerevisiae Proteins
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
801Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M025748/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M025756/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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