The Mitochondrial Battleground: A Review of Microplastic-Induced Oxidative Stress and Inflammatory Pathways in Human Health

Abstract

This review synthesizes research on mechanisms of microplastic-induced mitochondrial damage, focusing on oxidative stress and inflammation to address the mechanistic pathways linking microplastic exposure to mitochondrial dysfunction and cellular toxicity. Analysis of diverse in vitro and in vivo studies across aquatic, terrestrial, and mammalian systems was conducted, emphasizing molecular, cellular, and functional mitochondrial parameters. Findings reveal consistent microplastic-induced reactive oxygen species generation, disrupting mitochondrial membrane potential and bioenergetics, with smaller and aged particles exerting greater toxicity. Inflammatory signalling via NF-κB, the NLRP3 inflammasome, and immune cell necroptosis is closely associated with oxidative stress, forming a feedback loop that exacerbates mitochondrial impairment. Molecular mechanisms implicate endocytic uptake pathways, mitochondrial calcium dysregulation, and apoptosis-related cascades, though causal validation remains limited. The interplay between oxidative stress and inflammation emerges as a central driver of mitochondrial damage across models. These integrated insights highlight the critical influence of microplastic physicochemical properties and biological context on mitochondrial and inflammatory responses. The findings inform future mechanistic research and underscore the need for standardized models to assess microplastic toxicity, advancing understanding of environmental and human health risks associated with microplastic pollution.