title: Balance is the challenge--the impact of mitochondrial dynamics in Parkinson's disease.
abstract: Impaired mitochondrial function has been implicated in neurodegeneration in Parkinson's disease (PD) based on biochemical and pathoanatomical studies in brains of PD patients. This observation was further substantiated by the identification of exogenic toxins, i.e. complex I inhibitors that directly affect mitochondrial energy metabolism and cause Parkinsonism in humans and various animal models. Recently, insights into the underlying molecular signalling pathways leading to alterations in mitochondrial homeostasis were gained based on the functional characterization of mitoprotective genes identified in rare forms of inherited PD. Using in vitro and in vivo loss of function models of the Parkin, PINK1, DJ-1 and Omi/HtrA2 gene, the emerging field of mitochondrial dynamics in PD was established as being critical for the maintenance of mitochondrial function in neurons. This underscored the concept that mitochondria are highly dynamic organelles, which are tightly regulated to continuously adapt shape to functional and anatomical requirements during axonal transport, synaptic signalling, organelle degradation and cellular energy supply. The dissection of pathways involved in mitochondrial quality control clearly established the PINK1/Parkin-pathway in the clearance of dysfunctional mitochondria by autophagy and hints to a complex interplay between PD-associated proteins acting at the mitochondrial interface. The elucidation of this mitoprotective signalling network may help to define novel therapeutic targets for PD via molecular modelling of mitochondria and/or pharmacological modulation of mitochondrial dynamics.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany DZNE, German.
authors.forename: Lena F
authors.initials: LF
authors.lastname: Burbulla
authors.forename: Guido
authors.initials: G
authors.lastname: Krebiehl
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
mesh_terms: D001343:Autophagy / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics