Authors
Yoshida, A., Yamamoto, H., Miyata, T., Tomita, T., Yoshida, M., Namba, K., Kosono, S., Nishiyama, M.
Abstract
CoA transferases play essential roles in short-chain fatty acid metabolism by catalyzing the reversible transfer of CoA groups between acyl substrates. However, how their activities are regulated in response to cellular metabolic states remains unclear. Here we identify a dual regulatory mechanism of a CoA transferase from Thermus thermophilus, which is controlled by both interaction with an NAD+-sensing accessory protein and protein acetylation. The enzyme associates with an alanine dehydrogenase-like protein that lacks catalytic activity but binds NAD+ and NADH. Biochemical analyses revealed that inhibition occurs specifically upon NAD+ binding, but not NADH, indicating that the alanine dehydrogenase-like protein senses the intracellular NAD+/NADH ratio. Cryo-electron microscopy structures of the complex of CoA transferase and alanine dehydrogenase-like protein reveal the structural basis of this redox-dependent inhibition. Furthermore, acetylation of the CoA transferase alleviates the inhibition. Since the NAD+/NADH ratio and acetyl-CoA levels reflect the cellular energy and metabolic states, these findings uncover a previously unrecognized regulatory link through which redox sensing and acetylation cooperate to fine-tune the {beta}-oxidation flux.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Nov 2025.
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