Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration.
Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations o...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3554762?pdf=render |
| _version_ | 1811196181977497600 |
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| author | M Cristina Kenney Marilyn Chwa Shari R Atilano Janelle M Pavlis Payam Falatoonzadeh Claudio Ramirez Deepika Malik Tiffany Hsu Grace Woo Kyaw Soe Anthony B Nesburn David S Boyer Baruch D Kuppermann S Michal Jazwinski Michael V Miceli Douglas C Wallace Nitin Udar |
| author_facet | M Cristina Kenney Marilyn Chwa Shari R Atilano Janelle M Pavlis Payam Falatoonzadeh Claudio Ramirez Deepika Malik Tiffany Hsu Grace Woo Kyaw Soe Anthony B Nesburn David S Boyer Baruch D Kuppermann S Michal Jazwinski Michael V Miceli Douglas C Wallace Nitin Udar |
| author_sort | M Cristina Kenney |
| collection | DOAJ |
| description | Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD).Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism.Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD. |
| first_indexed | 2024-04-12T00:55:27Z |
| format | Article |
| id | doaj.art-1e6297845c0d4c1bbfd598fd15860ca7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T00:55:27Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1e6297845c0d4c1bbfd598fd15860ca72022-12-22T03:54:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5433910.1371/journal.pone.0054339Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration.M Cristina KenneyMarilyn ChwaShari R AtilanoJanelle M PavlisPayam FalatoonzadehClaudio RamirezDeepika MalikTiffany HsuGrace WooKyaw SoeAnthony B NesburnDavid S BoyerBaruch D KuppermannS Michal JazwinskiMichael V MiceliDouglas C WallaceNitin UdarMitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD).Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism.Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD.http://europepmc.org/articles/PMC3554762?pdf=render |
| spellingShingle | M Cristina Kenney Marilyn Chwa Shari R Atilano Janelle M Pavlis Payam Falatoonzadeh Claudio Ramirez Deepika Malik Tiffany Hsu Grace Woo Kyaw Soe Anthony B Nesburn David S Boyer Baruch D Kuppermann S Michal Jazwinski Michael V Miceli Douglas C Wallace Nitin Udar Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. PLoS ONE |
| title | Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. |
| title_full | Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. |
| title_fullStr | Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. |
| title_full_unstemmed | Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. |
| title_short | Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration. |
| title_sort | mitochondrial dna variants mediate energy production and expression levels for cfh c3 and efemp1 genes implications for age related macular degeneration |
| url | http://europepmc.org/articles/PMC3554762?pdf=render |
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