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Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences

Nicole Exner, Anne Kathrin Lutz, Christian Haass, Konstanze F Winklhofer

Author Affiliations

  1. Nicole Exner1,
  2. Anne Kathrin Lutz2,3,
  3. Christian Haass1,3 and
  4. Konstanze F Winklhofer*,2,3
  1. 1 Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
  2. 2 Munich, Germany
  3. 3 Munich, Germany
  1. *Corresponding author. Neurobiochemistry, German Center for Neurodegenerative Diseases (DZNE) Munich, Schillerstrasse 44, Munich 80336, Germany. Tel.:+49 89 2180 75483; Fax:+49 89 2180 75415; E-mail: Konstanze.Winklhofer{at}med.uni-muenchen.de
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Abstract

Neurons are critically dependent on mitochondrial integrity based on specific morphological, biochemical, and physiological features. They are characterized by high rates of metabolic activity and need to respond promptly to activity‐dependent fluctuations in bioenergetic demand. The dimensions and polarity of neurons require efficient transport of mitochondria to hot spots of energy consumption, such as presynaptic and postsynaptic sites. Moreover, the postmitotic state of neurons in combination with their exposure to intrinsic and extrinsic neuronal stress factors call for a high fidelity of mitochondrial quality control systems. Consequently, it is not surprising that mitochondrial alterations can promote neuronal dysfunction and degeneration. In particular, mitochondrial dysfunction has long been implicated in the etiopathogenesis of Parkinson's disease (PD), based on the observation that mitochondrial toxins can cause parkinsonism in humans and animal models. Substantial progress towards understanding the role of mitochondria in the disease process has been made by the identification and characterization of genes causing familial variants of PD. Studies on the function and dysfunction of these genes revealed that various aspects of mitochondrial biology appear to be affected in PD, comprising mitochondrial biogenesis, bioenergetics, dynamics, transport, and quality control.

  • Received March 15, 2012.
  • Accepted June 1, 2012.
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