Featured Review Cell Science Reviews Vol 6 No 2 ISSN 1742-8130

Mitochondrial dysfunction & Parkinson's Disease

There is growing evidence that mitochondrial dysfunction plays a pivotal role in the neuronal demise that occurs in many neurodegenerative diseases. The impact of dysfunctional mitochondria in neurodegeneration is twofold. First, disruption in energy and Ca²⁺ ion homeostasis mitigates the effectiveness of anti-oxidative defense and sensitizes the cells to apoptosis or necrosis. Second, the loss of mitochondrial membrane integrity also results in the release of proteins that initiate cell death pathways. These detrimental impacts of mitochondrial dysfunction are more relevant in post-mitotic neurons since they cannot dilute the number of malfunctioning mitochondria via cell division. Normally, an excess in the number of mitochondria and mtDNA copies in each mitochondrion are used to cushion fluctuating energy demand. Moreover, mitophagy and biogenesis together with fusion/fission activity are used to maintain mitochondrial homeostasis and to ensure neuronal survival. In dopaminergic neurons, complex I has been determined to have the lowest numbers of excess genetic copies, making its activity most prone to be affected and to cause mitochondrial dysfunction. A lower complex I activity has indeed been observed in postmortem brain tissues of PD patients. In this review, we will examine the physiology of mitochondria and dopaminergic neurons so as to explore the potential causes of mitochondrial dysfunction. In addition, the contribution of malfunctioning mitochondria to cell death will also be discussed. Finally, therapeutic strategies will be outlined.

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