PINK1 Deficiency Facilitates Palmitic Acid-Induced Inflammation by Disrupting Mitochondrial Function to Activate mtDNA-cGAS-STING Signaling

Abstract

Metabolic cells exhibit low-grade chronic inflsammation characterized by excessive production and secretion of proinflammatory cytokines and chemokines in response to overnutrition and energy excess. Mitochondrial dysfunction is closely associated with metabolic inflammation. PINK1 (phosphatase and tensin homology-induced putative kinase 1) is a crucial pathway controlling mitochondrial autophagy, essential for maintaining mitochondrial quality control and metabolic homeostasis. The aim of this study was to investigate the role of PINK1 in metabolic inflammation. Our findings indicate that in adipocytes, palmitic acid (PA) activates the expression of PINK1. Additionally, knockdown of PINK1 exacerbates PA-induced adipocyte inflammation. Mechanistically, PINK1 deficiency impairs mitochondrial function, leading to the release of mtDNA and further activation of the cGAS-STING pathway. Therefore, targeting mitochondrial autophagy in adipocytes and the cGAS-STING pathway may represent effective approaches to alleviate the chronic inflammation associated with obesity and related metabolic disorders.