Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B

J. J.David Ho, Nathan C. Balukoff, Grissel Cervantes, Petrice D. Malcolm, Jonathan R. Krieger, Stephen Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

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. Ho et al. employed MATRIX to demonstrate that eIF5B is an essential hypoxic translation factor that facilitates met-tRNAiMet delivery to ribosomes, serving as the hypoxic surrogate of the textbook eIF2. Aerobic eukarya likely retained eIF5B for the oxygen-dependent regulation of central carbon metabolism and hypoxic survival.

Original languageEnglish (US)
Pages (from-to)17-26
Number of pages10
JournalCell Reports
Volume22
Issue number1
DOIs
StatePublished - Jan 2 2018

Fingerprint

Eukaryotic Initiation Factors
Metabolism
Carbon
Oxygen
Ribosomes
Eukaryota
eukaryotic initiation factor-5B
Textbooks
Fractionation
Methionine
Yeast
Labeling
Machinery
Mass spectrometry
Reactive Oxygen Species
Mass Spectrometry
Yeasts
Cells

Keywords

  • ATF4
  • carbon metabolism
  • eIF5B
  • evolution
  • glycolysis
  • hypoxia
  • IF2
  • MATRIX
  • stress
  • translation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ho, J. J. D., Balukoff, N. C., Cervantes, G., Malcolm, P. D., Krieger, J. R., & Lee, S. (2018). Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B. Cell Reports, 22(1), 17-26. https://doi.org/10.1016/j.celrep.2017.12.031

Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B. / Ho, J. J.David; Balukoff, Nathan C.; Cervantes, Grissel; Malcolm, Petrice D.; Krieger, Jonathan R.; Lee, Stephen.

In: Cell Reports, Vol. 22, No. 1, 02.01.2018, p. 17-26.

Research output: Contribution to journalArticle

Ho, JJD, Balukoff, NC, Cervantes, G, Malcolm, PD, Krieger, JR & Lee, S 2018, 'Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B', Cell Reports, vol. 22, no. 1, pp. 17-26. https://doi.org/10.1016/j.celrep.2017.12.031
Ho, J. J.David ; Balukoff, Nathan C. ; Cervantes, Grissel ; Malcolm, Petrice D. ; Krieger, Jonathan R. ; Lee, Stephen. / Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B. In: Cell Reports. 2018 ; Vol. 22, No. 1. pp. 17-26.
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