Balance is the challenge – The impact of mitochondrial dynamics in Parkinson’s disease
Lena F. Burbulla,
Guido Krebiehl,
Rejko Krüger,
Lena F. Burbulla
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Graduate School of Cellular & Molecular Neuroscience, University of Tübingen, Germany
Search for more papers by this authorGuido Krebiehl
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Search for more papers by this authorRejko Krüger
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Search for more papers by this authorLena F. Burbulla,
Guido Krebiehl,
Rejko Krüger,
Lena F. Burbulla
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Graduate School of Cellular & Molecular Neuroscience, University of Tübingen, Germany
Search for more papers by this authorGuido Krebiehl
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Search for more papers by this authorRejko Krüger
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Search for more papers by this authorProfessor Dr. Rejko Krüger, MD, Laboratory of Functional Neurogenomics, Center of Neurology, Hertie-Institute for Clinical Brain Research and German Research Center for Neurogenerative Diseases (DZNE), Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. Tel.: +49-7071-2982141; fax: +49-7071-295260; e-mail: [email protected]
Abstract
Eur J Clin Invest 2010; 40 (11): 1048–1060
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.
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