“Paleoartists” attempt to hone their craft and captivate the public even as they grapple with emerging data that alter how we see dinosaurs.
Image credit: Mark Witton.
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
Edited by Barry Ganetzky, University of Wisconsin, Madison, WI, and approved May 9, 2012 (received for review December 15, 2011)
Abstract
Studies of the familial Parkinson disease-related proteins PINK1 and Parkin have demonstrated that these factors promote the fragmentation and turnover of mitochondria following treatment of cultured cells with mitochondrial depolarizing agents. Whether PINK1 or Parkin influence mitochondrial quality control under normal physiological conditions in dopaminergic neurons, a principal cell type that degenerates in Parkinson disease, remains unclear. To address this matter, we developed a method to purify and characterize neural subtypes of interest from the adult Drosophila brain. Using this method, we find that dopaminergic neurons from Drosophila parkin mutants accumulate enlarged, depolarized mitochondria, and that genetic perturbations that promote mitochondrial fragmentation and turnover rescue the mitochondrial depolarization and neurodegenerative phenotypes of parkin mutants. In contrast, cholinergic neurons from parkin mutants accumulate enlarged depolarized mitochondria to a lesser extent than dopaminergic neurons, suggesting that a higher rate of mitochondrial damage, or a deficiency in alternative mechanisms to repair or eliminate damaged mitochondria explains the selective vulnerability of dopaminergic neurons in Parkinson disease. Our study validates key tenets of the model that PINK1 and Parkin promote the fragmentation and turnover of depolarized mitochondria in dopaminergic neurons. Moreover, our neural purification method provides a foundation to further explore the pathogenesis of Parkinson disease, and to address other neurobiological questions requiring the analysis of defined neural cell types.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: pallanck{at}u.washington.edu.
Author contributions: J.L.B., A.C.P., and L.P. designed research; J.L.B., S.Y., A.C.P., and R.B.D. performed research; J.L.B., A.C.P., and L.P. contributed new reagents/analytic tools; J.L.B. and L.P. analyzed data; and J.L.B. and L.P. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1120688109/-/DCSupplemental.
Mitochondrial dysfunction in dopaminergic neurons
Sign up for Article Alerts
Article Classifications
- Biological Sciences
- Genetics
Jump to section
You May Also be Interested in
Coral reef bleaching frequently makes headlines, but researchers are still trying to sort out the cellular mechanisms at work.
Image credit: The Ocean Agency/XL Catlin Seaview Survey.
Greenhouse gas emissions in the first decades of the 21st century are likely to affect global sea level for centuries, and limiting long-term sea-level rise might require stringent near-term emission reductions.
Image courtesy of Lucy Reading-Ikkanda (artist).
A single formulation combining two gene therapies treated an array of age-related disorders in mice.
Image courtesy of Pixabay/Sipa.
Many ecosystems in the United States may be vulnerable to increased fire occurrence and frequency caused by invasive grasses.
Image courtesy of Pixabay/Stevepb.