Micro- and nanoplastic-induced mitochondrial dysfunction and organelle miscommunication: A toxicological perspective

Microplastics and nanoplastics (MNPs) and their derivatives, pose significant environmental and biomedical risks due to their pronounced cellular toxicity. These particulates disrupt mitochondrial function and compromise inter-organelle communication, leading to enhanced oxidative stress, calcium dysregulation, impaired ATP production, and activation of cellular stress responses including mitophagy and apoptosis. Mitochondrial dysfunction extends its impact to other organelles such as lysosomes, the endoplasmic reticulum (ER), and the nucleus, resulting in impaired organelle crosstalk, epigenetic modifications, and genomic instability. Plastic additives and adsorbed pollutants exacerbate these effects, further destabilizing cellular homeostasis and contributing to systemic pathologies encompassing metabolic disorders, neurodegeneration, cardiovascular dysfunction, and reproductive toxicity. This review synthesizes current mechanistic insights into the pathways mediating MNPs-induced mitochondrial and organelle dysfunction, emphasizing the critical role of disrupted mitochondrial dynamics, ER stress, and bioenergetic failure. Therapeutic strategies focusing on mitochondria-targeted antioxidants, ER stress modulators, and autophagy regulators show promise but require validation under environmentally relevant conditions. Addressing notable research gaps such as polymer diversity, chronic low-dose exposure, and co-contaminant effects through integrative, multi-disciplinary approaches will enhance understanding of long-term health impacts and inform effective mitigation strategies against the pervasive threat of MNPs pollution.