Parkinson's disease (PD) is a progressive neurodegenerative disorder linked to mitochondrial dysfunction and inhibition of the electron transport chain. This dysfunction leads to reactive oxygen species (ROS) generation and energy depletion, causing oxidative stress and excitotoxicity, which contribute to neuronal death in the substantia nigra pars compacta (SNpc). Genetic studies show that several genes associated with inherited PD encode mitochondrial proteins or those involved in mitochondrial dysfunction. Environmental toxins that inhibit the mitochondrial respiratory chain are also linked to PD. Mitochondria are essential for energy production and regulate apoptosis, calcium homeostasis, and iron-sulphur cluster formation. Mitochondrial DNA (mtDNA) is susceptible to damage from free radicals, leading to mutations associated with PD. The electron transport chain (ETC) consists of five complexes, with Complex I deficiency being a key factor in PD. Dysfunction in Complex I and III leads to increased ROS production, oxidative stress, and excitotoxicity. ROS can cause protein damage, lipid peroxidation, and DNA damage, contributing to PD pathology. Iron accumulation in PD is linked to oxidative stress. Calcium dysregulation, particularly through excitotoxicity, exacerbates mitochondrial dysfunction. Dopamine metabolism generates oxidative stress, which may contribute to PD. Genetic links between mitochondrial dysfunction and PD include α-synuclein, Parkin, PINK1, and DJ-1. Mutations in these genes are associated with mitochondrial dysfunction and PD. mtDNA mutations also play a role in PD. Lewy bodies (LBs) are intraneuronal inclusions containing α-synuclein, ubiquitin, and neurofilaments. Mitochondria are involved in LB formation and proteasomal functions. Neurotoxins like MPTP, rotenone, paraquat, diquat, and TaClo cause mitochondrial dysfunction and PD-like symptoms. These toxins inhibit Complex I, leading to ROS production and neuronal death. Environmental and genetic factors combine to cause mitochondrial dysfunction, leading to ROS and excitotoxicity-mediated DA cell death in PD. Further research is needed to fully understand the mechanisms linking mitochondrial dysfunction to PD.Parkinson's disease (PD) is a progressive neurodegenerative disorder linked to mitochondrial dysfunction and inhibition of the electron transport chain. This dysfunction leads to reactive oxygen species (ROS) generation and energy depletion, causing oxidative stress and excitotoxicity, which contribute to neuronal death in the substantia nigra pars compacta (SNpc). Genetic studies show that several genes associated with inherited PD encode mitochondrial proteins or those involved in mitochondrial dysfunction. Environmental toxins that inhibit the mitochondrial respiratory chain are also linked to PD. Mitochondria are essential for energy production and regulate apoptosis, calcium homeostasis, and iron-sulphur cluster formation. Mitochondrial DNA (mtDNA) is susceptible to damage from free radicals, leading to mutations associated with PD. The electron transport chain (ETC) consists of five complexes, with Complex I deficiency being a key factor in PD. Dysfunction in Complex I and III leads to increased ROS production, oxidative stress, and excitotoxicity. ROS can cause protein damage, lipid peroxidation, and DNA damage, contributing to PD pathology. Iron accumulation in PD is linked to oxidative stress. Calcium dysregulation, particularly through excitotoxicity, exacerbates mitochondrial dysfunction. Dopamine metabolism generates oxidative stress, which may contribute to PD. Genetic links between mitochondrial dysfunction and PD include α-synuclein, Parkin, PINK1, and DJ-1. Mutations in these genes are associated with mitochondrial dysfunction and PD. mtDNA mutations also play a role in PD. Lewy bodies (LBs) are intraneuronal inclusions containing α-synuclein, ubiquitin, and neurofilaments. Mitochondria are involved in LB formation and proteasomal functions. Neurotoxins like MPTP, rotenone, paraquat, diquat, and TaClo cause mitochondrial dysfunction and PD-like symptoms. These toxins inhibit Complex I, leading to ROS production and neuronal death. Environmental and genetic factors combine to cause mitochondrial dysfunction, leading to ROS and excitotoxicity-mediated DA cell death in PD. Further research is needed to fully understand the mechanisms linking mitochondrial dysfunction to PD.