title: A new link to mitochondrial impairment in tauopathies.
abstract: Tauopathies like the "frontotemporal dementia with Parkinsonism linked to chromosome 17" (FTDP-17) are characterized by an aberrant accumulation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau. For FTDP-17, a pathogenic tau mutation P301L was identified. Impaired mitochondrial function including disturbed dynamics such as fission and fusion are most likely major pathomechanisms of most neurodegenerative diseases. However, very little is known if tau itself affects mitochondrial function and dynamics. We addressed this question using SY5Y cells stably overexpressing wild-type (wt) and P301L mutant tau. P301L overexpression resulted in a substantial complex I deficit accompanied by decreased ATP levels and increased susceptibility to oxidative stress. This was paralleled by pronounced changes in mitochondrial morphology, decreased fusion and fission rates accompanied by reduced expression of several fission and fusion factors like OPA-1 or DRP-1. In contrast, overexpression of wt tau exhibits protective effects on mitochondrial function and dynamics including enhanced complex I activity. Our findings clearly link tau bidirectional to mitochondrial function and dynamics, identifying a novel aspect of the physiological role of tau and the pathomechanism of tauopathies.
authors: Department of Pharmacology, ZAFES, Biocenter, University of Frankfurt, 60438 Frankfurt, Germany.
authors: Kathrin L
authors: KL
authors: Schulz
authors: Anne
authors: A
authors: Eckert
authors: Virginie
authors: V
authors: Rhein
authors: Sören
authors: S
authors: Mai
authors: Winfried
authors: W
authors: Haase
authors: Andreas S
authors: AS
authors: Reichert
authors: Marina
authors: M
authors: Jendrach
authors: Walter E
authors: WE
authors: Müller
authors: Kristina
authors: K
authors: Leuner
mesh_terms: D045744:Cell Line, Tumor; D004579:Electron Transport; D006801:Humans; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D016875:tau Proteins