Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B.
Cell Rep
; 22(1): 17-26, 2018 01 02.
Article
de En
| MEDLINE
| ID: mdl-29298419
ABSTRACT
The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of IF2, an ancient translation factor that enables initiator methionine-tRNAiMet (met-tRNAiMet) loading on prokaryotic ribosomes. While it can be traced back to the last universal common ancestor, eIF5B is curiously dispensable in modern aerobic yeast and mammalian cells. Here, we show that eIF5B is an essential element of the cellular hypoxic cap-dependent protein synthesis machinery. System-wide interrogation of dynamic translation machineries by MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) demonstrated augmented eIF5B activity in hypoxic translating ribosomes. Global translatome studies revealed central carbon metabolism, cellular hypoxic adaptation, and ATF4-mediated stress response as major eIF5B-dependent pathways. These primordial processes rely on eIF5B even in the presence of oxygen and active eIF2, the canonical recruiter of met-tRNAiMet in eukaryotes. We suggest that aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Oxygène
/
Biosynthèse des protéines
/
Carbone
/
Facteurs d'initiation eucaryotes
Type d'étude:
Diagnostic_studies
Limites:
Humans
Langue:
En
Journal:
Cell Rep
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique