Kir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters.

ABSTRACT: Immunometabolism contributes to inflammation, but how activated macrophages acquire extracellular nutrients to fuel inflammation is largely unknown. Here, we show that the plasma membrane potential (V_m) of macrophages mediated by Kir2.1, an inwardly-rectifying K⁺ channel, is an important determinant of nutrient acquisition and subsequent metabolic reprogramming promoting inflammation. In the absence of Kir2.1 activity, depolarized macrophage V_m lead to a caloric restriction state by limiting nutrient uptake and concomitant adaptations in nutrient conservation inducing autophagy, AMPK (Adenosine 5'-monophosphate-activated protein kinase), and GCN2 (General control nonderepressible 2), which subsequently depletes epigenetic substrates feeding histone methylat

SUBMITTER: Yu W 

PROVIDER: S-EPMC9213538 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature