ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 06, 2019
- Source ID
- 10.1038/s41467-019-11932-0
Entities
People
- Claudia Alves
- I-cheng Ho
- Jia-shu Yang
- Jia-wei Hsu
- Jian Li
- Ming Bai
- Seung-yeol Park
- Stella Y. Lee
- Victor W. Hsu
- William Tseng
- Xavier Michelet
Organizations
- National Institutes of Health
- United States Department of Defense