Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.
Mutations in mitochondrial DNA polymerase (pol gamma) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial r...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-11-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2773408?pdf=render |
| _version_ | 1818611166799200256 |
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| author | Rehan M Baqri Brittany A Turner Mary B Rheuben Bradley D Hammond Laurie S Kaguni Kyle E Miller |
| author_facet | Rehan M Baqri Brittany A Turner Mary B Rheuben Bradley D Hammond Laurie S Kaguni Kyle E Miller |
| author_sort | Rehan M Baqri |
| collection | DOAJ |
| description | Mutations in mitochondrial DNA polymerase (pol gamma) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol gamma deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol gamma-alpha mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases. |
| first_indexed | 2024-12-16T15:26:01Z |
| format | Article |
| id | doaj.art-014ab543816d4221836660ebed07c407 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T15:26:01Z |
| publishDate | 2009-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-014ab543816d4221836660ebed07c4072022-12-21T22:26:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-11-01411e787410.1371/journal.pone.0007874Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.Rehan M BaqriBrittany A TurnerMary B RheubenBradley D HammondLaurie S KaguniKyle E MillerMutations in mitochondrial DNA polymerase (pol gamma) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol gamma deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol gamma-alpha mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases.http://europepmc.org/articles/PMC2773408?pdf=render |
| spellingShingle | Rehan M Baqri Brittany A Turner Mary B Rheuben Bradley D Hammond Laurie S Kaguni Kyle E Miller Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. PLoS ONE |
| title | Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. |
| title_full | Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. |
| title_fullStr | Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. |
| title_full_unstemmed | Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. |
| title_short | Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. |
| title_sort | disruption of mitochondrial dna replication in drosophila increases mitochondrial fast axonal transport in vivo |
| url | http://europepmc.org/articles/PMC2773408?pdf=render |
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