Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe²⁺ through TRPML1 channel.

ABSTRACT: Lysosomes are best known for their roles in inflammatory responses by engaging in autophagy to remove inflammasomes. Here, we describe an unrecognized role for the lysosome, showing that it finely controls macrophage inflammatory function by manipulating the lysosomal Fe²⁺-prolyl hydroxylase domain enzymes (PHDs)-NF-κB-interleukin 1 beta (IL1B) transcription pathway that directly links lysosomes with inflammatory responses. TRPML1, a lysosomal cationic channel, is activated secondarily to ROS elevation upon inflammatory stimuli, which in turn suppresses IL1B transcription, thus limiting the excessive production of IL-1β in macrophages. Mechanistically, the suppression of IL1B transcription caused by TRPML1 activation results from its modulation on the release of lysosomal Fe

SUBMITTER: Xing Y 

PROVIDER: S-EPMC11760952 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature