Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 31, Pages 12937-12942Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1103295108
Keywords
mitochondrial DNA; mitochondrial biogenesis; oxidative phosphorylation
Categories
Funding
- National Institutes of Health-Karolinska Institute
- Swedish Research Council, Swedish Brain Power [K2011-62X-21870-01-6, K2009-61X-03185-39-3]
- Parkinson Foundation
- Karolinska Institute
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Mitochondrial dysfunction is heavily implicated in Parkinson disease (PD) as exemplified by the finding of an increased frequency of respiratory chain-deficient dopamine (DA) neurons in affected patients. An inherited form of PD is caused by impaired function of Parkin, an E3 ubiquitin ligase reported to translocate to defective mitochondria in vitro to facilitate their clearance. We have developed a reporter mouse to assess mitochondrial morphology in DA neurons in vivo and show here that respiratory chain deficiency leads to fragmentation of the mitochondrial network and to the formation of large cytoplasmic bodies derived from mitochondria. Surprisingly, the dysfunctional mitochondria do not recruit Parkin in vivo, and neither the clearance of defective mitochondria nor the neurodegeneration phenotype is affected by the absence of Parkin. We also show that anterograde axonal transport of mitochondria is impaired in respiratory chain-deficient DA neurons, leading to a decreased supply of mitochondria to the axonal terminals.
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