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

ABSTRACT: Aldehyde dehydrogenase 7A1 (ALDH7A1) is a metabolic enzyme that converts aldehydes to carboxylates. Here, we find that the reductive consequence of this catalytic activity, which generates NADH (nicotinamide adenine dinucleotide, reduced form) from NAD (nicotinamide adenine dinucleotide), 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 the fission stage. 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 uncover a non-canonical function of ALDH7A1, and also an unexpected way that NADH acts in cellular energetics. Moreover, the findings advance the understanding of intracellular transport by elucidating how multiple pathways can be coordinated, as well as defining physiologic circumstances in which this coordination occurs.

INSTRUMENT(S):

ORGANISM(S): Rattus Rattus (black Rat)

TISSUE(S): Liver

SUBMITTER: Joao Paulo  

LAB HEAD: Jiashu Yang

PROVIDER: PXD014645 | Pride | 2019-09-12

REPOSITORIES: Pride