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

Trends Neurosci. 2013 Jun;36(6):325-35. doi: 10.1016/j.tins.2013.03.002. Epub 2013 Apr 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / physiology
  • Animals
  • Axonal Transport
  • Charcot-Marie-Tooth Disease / genetics
  • Dynamins
  • Energy Metabolism
  • GTP Phosphohydrolases / deficiency
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / physiology*
  • Humans
  • Membrane Fusion
  • Membrane Proteins / physiology
  • Mice
  • Microtubule-Associated Proteins / physiology*
  • Mitochondria / physiology*
  • Mitochondria / ultrastructure
  • Mitochondrial Membrane Transport Proteins / physiology
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology*
  • Models, Neurological
  • Nerve Tissue Proteins / physiology*
  • Neurodegenerative Diseases / metabolism
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Receptors, Metabotropic Glutamate / physiology
  • Synapses / physiology
  • tau Proteins / physiology

Substances

  • Amyloid beta-Peptides
  • FIS1 protein, human
  • FIS1 protein, mouse
  • MAPT protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • Receptors, Metabotropic Glutamate
  • tau Proteins
  • Adenosine Triphosphate
  • GTP Phosphohydrolases
  • MFN2 protein, human
  • Mfn1 protein, mouse
  • Mfn2 protein, mouse
  • OPA1 protein, human
  • Mfn1 protein, human
  • DNM1L protein, human
  • Dynamins