Bioenergetics: Open Access

Significance of Mitochondrial Dysfunction in Parkinson's Disease

Alferds Brian^* Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
^*Correspondence: Alferds Brian, Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden, Email:

Received: 02-Jan-2023, Manuscript No. BEG-23-20594; Editor assigned: 04-Jan-2023, Pre QC No. BEG-23-20594 (PQ); Reviewed: 18-Jan-2023, QC No. BEG-23-20594; Revised: 25-Jan-2023, Manuscript No. BEG-23-20594 (R); Published: 02-Feb-2023, DOI: 10.35248/2167-7662.23.11.196

Description

Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disorder that affects about 1% of individuals aged 60 years and older. It is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor symptoms such as tremors, rigidity, and bradykinesia. However, the pathogenesis of PD is complex and involves various factors, including genetic, environmental, and mitochondrial dysfunction.

Mitochondria are essential organelles responsible for energy production, calcium homeostasis, and apoptosis regulation. They are dynamic structures that undergo fusion and fission events, which play a crucial role in maintaining their function and integrity. Mitochondrial dysfunction has been implicated in the pathogenesis of several neurodegenerative disorders, including PD.

Mitochondrial dysfunction in Parkinson's disease

The involvement of mitochondrial dysfunction in PD was first proposed in the 1980s when it was observed that PD patients had reduced activity of mitochondrial respiratory chain complex I in the substantia nigra. Since then, numerous studies have confirmed the role of mitochondrial dysfunction in PD pathogenesis.

There is evidence to suggest that mitochondrial malfunction contributes to Parkinson's Disease (PD). Firstly, mutations in genes that encode proteins involved in mitochondrial function, such as PINK1, Parkin, and DJ-1, have been associated with familial forms of PD. PINK1 and Parkin are involved in mitophagy, a process by which damaged mitochondria are selectively degraded, while DJ-1 plays a role in mitochondrial respiration and Reactive Oxygen Species (ROS) detoxification.

Secondly, studies using neurotoxins that specifically target complex I of the mitochondrial respiratory chain, such as rotenone and Mitochondrial Permeability Transition Pore (MPTP), have been shown to induce dopaminergic neuron degeneration and motor deficits in animal models. These toxins impair mitochondrial function by inhibiting complex I activity, leading to the accumulation of ROS and oxidative stress.

Thirdly, post-mortem studies have shown that PD patients have decreased mitochondrial respiratory chain complex I activity and increased oxidative damage in the substantia nigra. Additionally, electron microscopy studies have revealed that PD patients have abnormal mitochondrial morphology and distribution in affected brain regions.

Mitochondrial dysfunction and oxidative stress in Parkinson’s disease

One of the potential mechanisms by which mitochondrial dysfunction contributes to PD pathogenesis is through the generation of oxidative stress. Mitochondria are the main source of ROS in cells, and impaired mitochondrial function can lead to an increase in ROS production, which can damage cellular components such as DNA, proteins, and lipids.

In PD, increased oxidative stress has been observed in affected brain regions, and several markers of oxidative damage, such as protein carbonyls, lipid peroxidation products, and DNA oxidation products, have been found in PD patients' substantia nigra. Additionally, decreased activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase has been observed in PD patients, further exacerbating oxidative damage.

Mitochondrial dysfunction and apoptosis in Parkinson’s disease

Another potential mechanism by which mitochondrial dysfunction contributes to PD pathogenesis is through the induction of apoptosis. Mitochondria play a crucial role in apoptosis regulation, and dysfunction in this process can lead to cell death.

In PD, the accumulation of damaged mitochondria and the subsequent release of pro-apoptotic factors, such as cytochrome c, can trigger the activation of the intrinsic apoptotic pathway. This can lead to the activation of caspases, which are proteases that cleave cellular components, ultimately leading to cell death.