Link of impaired metal ion homeostasis to mitochondrial dysfunction in neurons.

Manganese, iron, copper, and zinc are observed to play essential roles in mitochondria. The overload and depletion of metal ions in mitochondria under pathological conditions, however, could disturb mitochondrial compartments and functions leading to cell death. In this review, we mainly summarize how impaired metal ion homeostasis affects mitochondrial systems, such as membrane potentials, the tricarboxylic acid cycle, oxidative phosphorylation, and glutathione metabolism. In addition, based on current findings, we briefly describe a recent understanding of the relationship among metal ion dysregulation, mitochondrial dysfunction, and the pathogeneses of neurodegenerative diseases.