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GAPDH 在细胞能量稳态饥饿期间抑制细胞内途径。

GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis.

机构信息

Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

Nature. 2018 Sep;561(7722):263-267. doi: 10.1038/s41586-018-0475-6. Epub 2018 Sep 12.

DOI:10.1038/s41586-018-0475-6
PMID:30209366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6152935/
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, 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.

摘要

饥饿对细胞存活构成了根本性的挑战。虽然自噬在促进这种环境下的能量平衡方面的作用已经得到了广泛的描述，但其他机制的了解较少。在这里，我们揭示了甘油醛 3-磷酸脱氢酶 (GAPDH) 通过将 GTP 酶激活蛋白 (GAP) 靶向 ADP-核糖基化因子 1 (ARF1) 来抑制 COPI 运输，从而抑制 COPI 囊泡裂变。GAPDH 还通过靶向 ARF GAP 来抑制多种其他运输途径。进一步的表征表明，这种广泛的抑制是细胞在饥饿期间激活的，以减少能量消耗。这些发现揭示了细胞内运输途径之间存在着显著的协调水平，这是细胞能量平衡的一个关键机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/9c24a1470070/nihms-981559-f0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/8ca3f183d514/nihms-981559-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/285ef6dc9b16/nihms-981559-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/cc893d78f8b7/nihms-981559-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/ce8e17ebe34f/nihms-981559-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/fedf35332f64/nihms-981559-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/3c16bd2bfdae/nihms-981559-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/32de90d89249/nihms-981559-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e22/6152935/7bf3f9ab6e58/nihms-981559-f0012.jpg
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