Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients
Mutations in the parkin gene are the most common cause of early-onset Parkinson’s disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigati...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2016/1819209 |
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| author | William Haylett Chrisna Swart Francois van der Westhuizen Hayley van Dyk Lize van der Merwe Celia van der Merwe Ben Loos Jonathan Carr Craig Kinnear Soraya Bardien |
| author_facet | William Haylett Chrisna Swart Francois van der Westhuizen Hayley van Dyk Lize van der Merwe Celia van der Merwe Ben Loos Jonathan Carr Craig Kinnear Soraya Bardien |
| author_sort | William Haylett |
| collection | DOAJ |
| description | Mutations in the parkin gene are the most common cause of early-onset Parkinson’s disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigating the mitochondrial functions of parkin. However, published results reporting on patient-derived parkin-mutant fibroblasts have been inconsistent. This study aimed to functionally compare parkin-mutant fibroblasts from PD patients with wild-type control fibroblasts using a variety of assays to gain a better understanding of the role of mitochondrial dysfunction in PD. To this end, dermal fibroblasts were obtained from three PD patients with homozygous whole exon deletions in parkin and three unaffected controls. Assays of mitochondrial respiration, mitochondrial network integrity, mitochondrial membrane potential, and cell growth were performed as informative markers of mitochondrial function. Surprisingly, it was found that mitochondrial respiratory rates were markedly higher in the parkin-mutant fibroblasts compared to control fibroblasts (p = 0.0093), while exhibiting more fragmented mitochondrial networks (p=0.0304). Moreover, cell growth of the parkin-mutant fibroblasts was significantly higher than that of controls (p=0.0001). These unanticipated findings are suggestive of a compensatory mechanism to preserve mitochondrial function and quality control in the absence of parkin in fibroblasts, which warrants further investigation. |
| format | Article |
| id | doaj-art-42afefd13d1d4b64b50240fedef33f16 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-42afefd13d1d4b64b50240fedef33f162025-02-03T01:25:05ZengWileyParkinson's Disease2090-80832042-00802016-01-01201610.1155/2016/18192091819209Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease PatientsWilliam Haylett0Chrisna Swart1Francois van der Westhuizen2Hayley van Dyk3Lize van der Merwe4Celia van der Merwe5Ben Loos6Jonathan Carr7Craig Kinnear8Soraya Bardien9Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South AfricaCentre for Human Metabolomics, Faculty of Natural Sciences, North-West University, Potchefstroom, South AfricaCentre for Human Metabolomics, Faculty of Natural Sciences, North-West University, Potchefstroom, South AfricaDepartment of Statistics, University of the Western Cape, Cape Town, South AfricaDivision of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South AfricaDivision of Neurology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDivision of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDivision of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaMutations in the parkin gene are the most common cause of early-onset Parkinson’s disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigating the mitochondrial functions of parkin. However, published results reporting on patient-derived parkin-mutant fibroblasts have been inconsistent. This study aimed to functionally compare parkin-mutant fibroblasts from PD patients with wild-type control fibroblasts using a variety of assays to gain a better understanding of the role of mitochondrial dysfunction in PD. To this end, dermal fibroblasts were obtained from three PD patients with homozygous whole exon deletions in parkin and three unaffected controls. Assays of mitochondrial respiration, mitochondrial network integrity, mitochondrial membrane potential, and cell growth were performed as informative markers of mitochondrial function. Surprisingly, it was found that mitochondrial respiratory rates were markedly higher in the parkin-mutant fibroblasts compared to control fibroblasts (p = 0.0093), while exhibiting more fragmented mitochondrial networks (p=0.0304). Moreover, cell growth of the parkin-mutant fibroblasts was significantly higher than that of controls (p=0.0001). These unanticipated findings are suggestive of a compensatory mechanism to preserve mitochondrial function and quality control in the absence of parkin in fibroblasts, which warrants further investigation.http://dx.doi.org/10.1155/2016/1819209 |
| spellingShingle | William Haylett Chrisna Swart Francois van der Westhuizen Hayley van Dyk Lize van der Merwe Celia van der Merwe Ben Loos Jonathan Carr Craig Kinnear Soraya Bardien Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients Parkinson's Disease |
| title | Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients |
| title_full | Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients |
| title_fullStr | Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients |
| title_full_unstemmed | Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients |
| title_short | Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson’s Disease Patients |
| title_sort | altered mitochondrial respiration and other features of mitochondrial function in parkin mutant fibroblasts from parkinson s disease patients |
| url | http://dx.doi.org/10.1155/2016/1819209 |
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