Insights Into the Activity, Production, and Signaling Circuits of Homoserine Lactones in Mammalian Cells Publisher



Fateh S T ; Ziai S A
Source: iScience Published:2026

Abstract

Emerging evidence suggests that acyl homoserine lactones (AHLs), bacterial signaling metabolites, also play signaling roles in eukaryotic organisms, including human cells. Through a meta-analysis of prior investigations, we mapped the effects of AHLs and their signaling roles. Given their evolutionary significance and potential physiological roles, we further asked whether human cells possess the machinery to perceive and produce AHLs or similar compounds. AHLs commonly regulate pathways involved in cell-fate decisions, with RXRs and peroxisome proliferator-activated receptors (PPARs) identified as potential upstream AHL receptors. Structural specificity was supported by the observation that both the γ-butyrolactone ring and the acyl tail contribute to receptor affinity. Furthermore, human glycine/glutamine acyltransferases showed structural and functional homology to bacterial AHL synthases using in silico analyses. Moreover, liquid chromatography-mass spectrometry of conditioned medium from two human cell lines suggested the production of potential AHLs. Together, this study proposes the possibility of an AHL-driven signaling circuit in human cells. © 2026 The Authors