GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis

Jia-Shu Yang, Jia-Wei Hsu, Seung-Yeol Park, Jian Li, William M. Oldham, Galina V. Beznoussenko, Alexander A. Mironov, Joseph Loscalzo and Victor W. Hsu ()
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Jia-Shu Yang: Brigham and Women’s Hospital and Harvard Medical School
Jia-Wei Hsu: Brigham and Women’s Hospital and Harvard Medical School
Seung-Yeol Park: Brigham and Women’s Hospital and Harvard Medical School
Jian Li: Brigham and Women’s Hospital and Harvard Medical School
William M. Oldham: Brigham and Women’s Hospital and Harvard Medical School
Galina V. Beznoussenko: The FIRC Institute of Molecular Oncology
Alexander A. Mironov: The FIRC Institute of Molecular Oncology
Joseph Loscalzo: Brigham and Women’s Hospital and Harvard Medical School
Victor W. Hsu: Brigham and Women’s Hospital and Harvard Medical School

Nature, 2018, vol. 561, issue 7722, 263-267

Abstract: Abstract Starvation poses a fundamental challenge to cell survival. Whereas the role of autophagy in promoting energy homeostasis in this setting has been extensively characterized1, 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.

Keywords: Coat Protein I (COPI); ADP-ribosylation Factor (ARF); ArfGAP; GAPDH S122; Endocytic Transport (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0475-6

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