FUN14 domain-containing 1-mediated mitophagy suppresses interleukin-1ß production in macrophages.

ABSTRACT

Mitochondria play a critical role in triggering immune response. Although recent evidence indicates that autophagy/mitophagy can suppress inflammation via regulation of mitochondrial homeostasis, limited information is available regarding physiological regulation of mitochondria-controlled inflammation. In this study, we investigated FUN14 domain containing 1 (FUNDC1)-mediated mitophagy in the regulation of interleukin-1ß (IL-1ß) in vitro and in vivo, wild-type FUNDC1 and its mitophagy defective Y18A/L21A mutant were analyzed in bone marrow-derived macrophages (BMDMs)for their effects on IL-1ß expression and mitochondrial damage. The current study identified that LPS plus nigericin stimulation induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, which was detected by IL-1ß expression. Moreover, FUNDC1-mediated mitophagy promoted the alleviation of intracellular reactive oxygen species (ROS). IL-1ß production was suppressed by the overexpression of wild-type FUNDC1, but not the Y18A/L21A mutant. Our results suggest that FUNDC1 suppresses LPS plus nigericin-mediated IL-1ß production through its regulatory effect on mitophagy, which will greatly promote the understanding of mitophagy-related protein in the regulation of immune response.