ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis

Jia-Shu Yang (), Jia-Wei Hsu, Seung-Yeol Park, Stella Y. Lee, Jian Li, Ming Bai, Claudia Alves, William Tseng, Xavier Michelet, I-Cheng Ho and Victor W. Hsu ()
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Jia-Shu Yang: Harvard Medical School
Jia-Wei Hsu: Harvard Medical School
Seung-Yeol Park: Harvard Medical School
Stella Y. Lee: Kansas State University
Jian Li: Harvard Medical School
Ming Bai: Harvard Medical School
Claudia Alves: Harvard Medical School
William Tseng: Harvard Medical School
Xavier Michelet: Harvard Medical School
I-Cheng Ho: Harvard Medical School
Victor W. Hsu: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract The aldehyde dehydrogenase (ALDH) family of metabolic enzymes converts aldehydes to carboxylates. Here, we find that the reductive consequence of ALDH7A1 activity, which generates NADH (nicotinamide adenine dinucleotide, reduced form) from NAD, underlies how ALDH7A1 coordinates a broad inhibition of the intracellular transport pathways. Studying vesicle formation by the Coat Protein I (COPI) complex, we elucidate that NADH generated by ALDH7A1 targets Brefeldin-A ADP-Ribosylated Substrate (BARS) to inhibit COPI vesicle fission. Moreover, defining a physiologic role for the broad transport inhibition exerted by ALDH7A1, we find that it acts to reduce energy consumption during hypoxia and starvation to promote cellular energy homeostasis. These findings advance the understanding of intracellular transport by revealing how the coordination of multiple pathways can be achieved, and also defining circumstances when such coordination is needed, as well as uncovering an unexpected way that NADH acts in cellular energetics.

Date: 2019
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DOI: 10.1038/s41467-019-11932-0

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