Abstract: Parkinson’s disease is the second most common progressive neurodegenerative disorder, after Alzheimer’s disease caused by the selective loss of dopaminergic neurons in the substantia nigra region of midrain. Clinical symptoms include resting tremor, bradykinesia, postural instability and rigidity. Although ageing, genetic and environmental factors have been suggested as the putative risk factors for the progression of the disease, the exact molecular mechanisms involved in the pathogenesis of the disease remains elusive. Mitochondria are the power house of the cell where generation of the ATP takes place. Recent studies have shown the importance of the mitochondrial dysfunction in the pathogenesis of the disease. A number of the mitochondrial neurotoxin like MPTP, paraquat, rotenone etc has been shown to induce the PD like features. Dysfunctional mitochondria release the cytochrome c in the cytosol which results in the death of the neurons through the apoptosis. Thus clearance of the dysfunctioned mitochondria can be regarded as a key event in the prevention of the PD. A number of mechanisms including fission, fusion, mitochondrial derived-vesicles formation have been reported in the maintainance of the mitochondrial quality of which mitophagy is most important in the clearance of the defective mitochondria. Mitophagy refers to the removal of the defective mitochondria through autophagy. Parkin and PINK 1 are two proteins function cooperatively in the clearance of the defective mitochondria during autophagy. A strong link of PINK 1/Parkin has been suggested with mitochondrial dysfunction, mitochondrial vesicular trafficking, mitochondrial dynamics, quality control and mitophagy. Pink1 is a ser- thr kinase which fuctions as sensor and detects the dysfunctioned mitochondria, after which it recruits cytosolic Parkin having E3 Ubiquitin ligase activity to depolarized mitochondria. Parkin then ubiquitinates the dysfunctiond mithochondria and directs them towards the autophagy for the clearance. Defects in the lysosomal-autophagy pathway or mutations in the PINK/ Parkin may result in poor clearing of the dysfunctioned mitochondria that ultimately results in the generation of the ROS generation and PD pathogenesis.

Keywords: Parkinson disease, Mitochondria, Autophagy, PINK1, Parkin, Mitochondria, Mitophagy, VDAC1, MDVs, UPS.

Downloads: | DOI: 10.17148/IARJSET.2026.13390