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.
Copyright © 2013 Elsevier Ltd. All rights reserved.
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