GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis.
basic_science · Level V
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- Record sourced from PubMed, PMID 30209366.
- Also identified by DOI 10.1038/s41586-018-0475-6 and PMC identifier 6152935.
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Abstract
Starvation poses a fundamental challenge to cell survival. Whereas the role of autophagy in promoting energy homeostasis in this setting has been extensively characterized<sup>1</sup>, other mechanisms are less well understood. Here we reveal that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibits coat protein I (COPI) transport by targeting a GTPase-activating protein (GAP) towards ADP-ribosylation factor 1 (ARF1) to suppress COPI vesicle fission. GAPDH inhibits multiple other transport pathways, also by targeting ARF GAPs. Further characterization suggests that this broad inhibition is activated by the cell during starvation to reduce energy consumption. These findings reveal a remarkable level of coordination among the intracellular transport pathways that underlies a critical mechanism of cellular energy homeostasis.
Medical subject headings
- Energy Metabolism
- Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
- Homeostasis