Immune cells use two different routes to produce acetyl-CoA, an essential metabolite required to fight infection and cancer, reports a study led by Van Andel Institute scientists. The findings, published in the Journal of Experimental Medicine , could help improve immunotherapies by revealing how diet can boost immune cell function . "Like any good system, immune cells have a plan A and a plan B," said Russell Jones, Ph.
D., the study's corresponding author and chair of VAI's Department of Metabolism and Nutritional Programming. "We've pinpointed how these cells use a two-pronged approach to ensure they have enough acetyl-CoA to do their jobs and keep us healthy.
Importantly, we gained new insights that may inform tailored dietary strategies for augmenting existing cancer treatments." Cells synthesize acetyl-CoA using nutrients, such as acetate, derived from food. When a threat is detected, cells add acetyl-CoA to certain proteins, which then unlock access to the genetic instructions required to fight disease and infection.
Insufficient acetyl-CoA derails the immune system's ability to protect the body. Until now, however, it was unclear exactly how immune cells maintained their acetyl-CoA reserves. In their new study, Jones and his colleagues identified two routes for acetyl-CoA production—a main route called ACLY and a backup route called ACSS2.
Cells prefer ACLY but, in the event of problems, ACSS2 picks up the slack to ensure a continual supply of acetyl-CoA. Although th.