Biologie cellulaire et du développement
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Mitochondrial Dysfunction and Mitophagy in Neurodegenerative Diseases

Kao LP and Wolvetang EJ

Mitochondria are critical in providing energy for neuronal development. They provide the majority of intracellular energy and perform important metabolic functions such as the Krebs cycle. Mitochondria contain their own mitochondrial DNA in a circular form, similar to bacterial genomes. Mitochondrial genomes encode several essential genes of the eukaryotic respiratory machinery, but most respiratory machinery components and factors controlling mitochondrial biogenesis are encoded in the nucleus. Mitochondria and the nucleus cooperate and communicate via retrograde signals, such as energy supply and redox signaling. This poorly understood communication is essential for balancing intracellular energy production and demand. Mitochondrial mutations could lead to dysfunctions in ATP production, calcium homeostasis, reactive oxygen species generation, and apoptotic signaling. Thus, mitochondrial dysfunction has been reported and discussed as part of neurodegenerative etiologies. There is no doubt that mitochondrial dysfunction, abnormal mitochondrial dynamics, and mitophagic degradation occur in neurodegenerative diseases. Mitochondrial turnover maintains cellular homeostasis by eliminating defective mitochondria through a specific form of autophagy, an evolutionarily conserved eukaryotic response to stress conditions by which lysosome contents are used to breakdown cytoplasmic proteins and organelles. Both number of ‘healthy’ and ‘mutated’ mitochondria could be increased or decreased by fusion and fission. Selective uptake of mitochondria by autophagosomes is called mitophagy. Mitophagic events are highly selective processes controlled by oxidative stress and are accompanied by loss of membrane potential and ensuing mitochondrial degradation. This review discusses the role of mitochondria in neurodegenerative diseases. This review also explores the connection between neurodegeneration and mitophagy, a highly selective autophagic process of oxidative stress-induced mitochondrial degradation. It will further discuss the role of fusion and fission processes in maintaining homeostasis.