Integrative Review of Mitochondrial Genes in Zebrafish Cardio hepatic Toxicity Induced by Microplastics, Nanoparticles and Xenobiotics

Abstract

Aquatic ecosystems are subject to escalating contamination by microplastics (MPs), engineered nanoparticles (NPs) and environmental xenobiotics yet the subcellular mechanisms through which these diverse contaminants converge to impair vertebrate organ function remain incompletely defined. This integrative review systematically examines the role of mitochondrial gene networks in mediating cardiohepatic toxicity in zebrafish (Danio rerio) exposed to MPs, NPs and xenobiotics drawing on evidence from transcriptomics, proteomics, metabolomics and functional mitochondrial biology. We demonstrate that across structurally diverse toxicant classes, a conserved molecular signature emerges comprising suppression of the PGC-1α/NRF1/TFAM biogenesis axis, transcriptional repression of both nuclear and mitochondrially encoded electron transport chain (ETC) subunits, dysregulation of mitochondrial fusion and fission dynamics, oxidative stress induced mtDNA damage and activation of the intrinsic apoptotic cascade. Toxicant class specific mechanisms metal ion mediated enzyme inhibition for metallic NPs, physical membrane intercalation for polymeric MPs and NPs, and CYP mediated bioactivation for xenobiotics which overlay these shared pathways generating mechanistically informative fingerprints for hazard characterization. The concurrent vulnerability of zebrafish cardiomyocytes and hepatocytes to mitochondrial dysfunction reflects their shared dependence on oxidative phosphorylation, high mitochondrial density and limited anaerobic capacity establishing the mechanistic basis of cardiohepatic toxicity crosstalk. Multi omics integration in zebrafish further reveals epigenetic propagation of mitochondrial dysfunction through CpG hypermethylation and histone remodelling at key biogenesis loci with potential transgenerational consequences. Validated mitochondrial biomarker panels including mtDNA copy number, ETC complex activities, ΔΨm and transcriptomic pathway scores which offer regulatory compatible endpoints for environmental risk assessment. These findings position zebrafish mitochondrial toxicogenomics as a powerful and translationally relevant platform for elucidating environment genome interactions underlying cardiovascular and hepatic disease in both aquatic biota and human populations.