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Protein Modifying Enzyme Ate1 Controls Cellular Warburg Effects
Author(s) -
Jiang Chunhua,
Birnbaum Michael,
Patel Devang,
Kumar Akhilesh,
Morgan William,
Lampidis Theodore,
Fontanesi Flavia,
Barrientos Antonio,
Zhang Fangliang
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.624.4
Subject(s) - biology , glycolysis , warburg effect , anaerobic glycolysis , oxidative phosphorylation , metabolism , microbiology and biotechnology , biochemistry , endocrinology , medicine
Protein arginylation by arginyl‐transfer RNA protein transferase (Ate1) is a post‐translational modification that targets a number of metabolic enzymes. However, the mechanisms and downstream effects of this modification in cellular metabolism are unknown. In this study, wild type mouse embryonic fibroblast cells (MEF‐WT) and Ate1 knockout mouse embryonic fibroblast cells (MEF‐KO) were used to measure several key metabolic parameters including glucose uptake, glucose starvation sensitivity, lactate production, cellular oxygen consumption rate (OCR). Ate1 is also down‐regulated by shRNA to repeat some of the above experiments. The results showed that Ate1‐KO MEF is more sensitive to glucose starvation than MEF‐WT, and that KO cells have significant higher glucose uptake and lactate production than MEF‐WT. Conversely, Ate1‐KO cells have lower cellular OCR than MEF‐WT. While the WT and Ate1‐KO cells have similar levels of cellular ATP, a significantly larger proportion of ATP in KO cells are derived from the glycolysis pathway. We further showed that this phenomenon can be repeated when Ate1 is down‐regulated by shRNA in WT cells, and that this phenotype can also be reversed when a recombinant Ate1 protein is reintroduced in the KO cells. CONCLUSION Our data suggest that knockout of Ate1 in MEF shift cellular metabolic pathways from mitochondrial oxidative phosphorylation to aerobic glycolysis, which is the sign of the Warburg effect. Support or Funding Information NIGMS (NIH), R01, # GM107333. DoD (CDMRP), Idea Award, PC140622 DoD (CDMRP), Exploratory Grant, PC141013