PINK1-mediated mitophagy reduced inflammatory responses to Porphyromonas gingivalis in macrophages.

Abstract

Mitochondria are strained by microbial stimuli in the periodontal niche. Damaged mitochondria are cleared by mitophagy. The purpose of the study was to explore whether mitophagy participated in the progress of periodontitis and whether activation of mitophagy can inhibit inflammatory responses to bacterial infection in macrophages. Mitophagy-related genes were measured in the healthy and inflamed human gingiva. Bone marrow-derived macrophages (BMDMs) were infected with Porphyromonas gingivalis. Dexmedetomidine, urolithin A, and resveratrol were used to activate mitophagy, while small interference RNA was utilized to knock down PTEN-induced putative protein kinase 1 (PINK1). Activation of mitophagy-related genes and colocalization of them were detected by Western blot and confocal imaging. Damages of mitochondria, accumulation of mitochondrial reactive oxygen species (mtROS), and production of IL-1β, IL-6, and TNF-α were measured. Levels of mitophagy-related genes were decreased in inflamed periodontal tissues and P.gingivalis-infected BMDMs. Dexmedetomidine, urolithin A, and resveratrol activated mitophagy, leading to reduced mitochondria damages, decreased mtROS generation, and inhibited IL-1β, IL-6, and TNF-α production. PINK1 knockdown reduced dexmedetomidine, urolithin A, and resveratrol-induced anti-inflammatory effect. Inhibited mitophagy participated in the progress of periodontitis. Activation of mitophagy may become a therapeutic target during the progress of periodontitis by reducing mtROS.