Why size matters - balancing mitochondrial dynamics in Alzheimer's disease

Abstract

Once perceived as solitary structures, mitochondria are now recognized as highly dynamic, interconnected organelles. The tight control of their fusion and fission, a process termed 'mitochondrial dynamics', is crucial for neurons, given their unique architecture and special energy and calcium-buffering requirements at the synapse. Interestingly, in Alzheimer's disease (AD), a condition initiated at the synapse, mitochondrial dynamics are severely impaired. Of the two proteins implicated in AD pathogenesis, amyloid-β (Aβ) and TAU, only the impact of Aβ on mitochondrial dynamics has been studied in detail. We highlight recent findings that TAU exerts a determinative effect in the regulation of mitochondrial dynamics, and therefore neuronal function. In this process, the GTPase DRP1 has emerged as a key target of both Aβ and TAU.