Differential production of superoxide by neuronal mitochondria
<p>Abstract</p> <p>Background</p> <p>Mitochondrial DNA (mtDNA) mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mu...
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| Format: | Article |
| Language: | English |
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BMC
2008-01-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/9/4 |
| _version_ | 1818389686855401472 |
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| author | Levin Leonard A Lieven Christopher J Hoegger Mark J |
| author_facet | Levin Leonard A Lieven Christopher J Hoegger Mark J |
| author_sort | Levin Leonard A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mitochondrial DNA (mtDNA) mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs), a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC) components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells.</p> <p>Results</p> <p>In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria.</p> <p>Conclusion</p> <p>RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.</p> |
| first_indexed | 2024-12-14T04:45:41Z |
| format | Article |
| id | doaj.art-eaf49276a3a54d44995ee7ed93a6ee02 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-14T04:45:41Z |
| publishDate | 2008-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-eaf49276a3a54d44995ee7ed93a6ee022022-12-21T23:16:41ZengBMCBMC Neuroscience1471-22022008-01-0191410.1186/1471-2202-9-4Differential production of superoxide by neuronal mitochondriaLevin Leonard ALieven Christopher JHoegger Mark J<p>Abstract</p> <p>Background</p> <p>Mitochondrial DNA (mtDNA) mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs), a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC) components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells.</p> <p>Results</p> <p>In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria.</p> <p>Conclusion</p> <p>RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.</p>http://www.biomedcentral.com/1471-2202/9/4 |
| spellingShingle | Levin Leonard A Lieven Christopher J Hoegger Mark J Differential production of superoxide by neuronal mitochondria BMC Neuroscience |
| title | Differential production of superoxide by neuronal mitochondria |
| title_full | Differential production of superoxide by neuronal mitochondria |
| title_fullStr | Differential production of superoxide by neuronal mitochondria |
| title_full_unstemmed | Differential production of superoxide by neuronal mitochondria |
| title_short | Differential production of superoxide by neuronal mitochondria |
| title_sort | differential production of superoxide by neuronal mitochondria |
| url | http://www.biomedcentral.com/1471-2202/9/4 |
| work_keys_str_mv | AT levinleonarda differentialproductionofsuperoxidebyneuronalmitochondria AT lievenchristopherj differentialproductionofsuperoxidebyneuronalmitochondria AT hoeggermarkj differentialproductionofsuperoxidebyneuronalmitochondria |