title: 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.
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Department of Pathology, Brigham and Women's Hospital, Harvard New Research Building, Room 630, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: DuBoff
authors.forename: Mel
authors.initials: M
authors.lastname: Feany
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000502:physiology; D000818:Animals; D001370:Axonal Transport; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D034281:Dynamins; D004734:Energy Metabolism; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D013569:Synapses / Q000502:physiology; D016875:tau Proteins / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; C476525:FIS1 protein, human; C561064:FIS1 protein, mouse; C054369:MAPT protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D018094:Receptors, Metabotropic Glutamate; D016875:tau Proteins; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse; C415198:OPA1 protein, human; C470017:Mfn1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins