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Iyer 2017 MiP2017
Coupling states LEAK  + , ROUTINE  +
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]] Mutations in the mitochondrial DNA (mtDNA) lead to many human mitochondrial disorders with impaired bioenergetics. The clinical severity of the disease may also depend on the load of mutant mtDNA and bioenergetic dysfunction. The development of FDA –approved therapies for primary mitochondrial disorders have been hindered by genetic and clinical heterogeneity, limited knowledge of natural history of disease progression, and lack of clear clinical endpoints. Our long-term goal is the development of patient- and disease-specific cell based models that will provide us novel insights into disease origins and severity. In this study, we have focused our efforts on Leigh’s syndrome (LS), as there is no current cure for LS nor an adequate model for understanding the rapid fatality associated with the disease. We characterized the mutation and mitochondrial function of two patient-derived fibroblasts from LS carrying T8993G point mutation encoding subunit of ATP synthase (Complex V); and T10185C point mutation encoding subunit of NADH dehydrogenase (Complex I). Using Sanger sequencing approaches, we confirmed the presence of the mutation in the patient fibroblasts. Immunocytochemical analysis based on use of MitoTracker Red CM-H2Xros and MitoTracker™ Green FM demonstrated that T8993G and T10185C cells have a low number of active mitochondria compared to healthy fibroblasts. Our preliminary observations indicate that the basal respiration and ATP production in the diseased cell lines were significantly lower than healthy fibroblast cells, while the proton leak and non-mitochondrial oxygen consumption of T8993G cells was higher compared to T10185C and healthy cells. Our findings demonstrate that both the patient fibroblasts have mitochondrial dysfunction that correlate with the pathogenic mtDNA burden. We are currently monitoring these parameters in the reprogrammed and differentiated cells carrying the mutation.
ifferentiated cells carrying the mutation.  +
Has editor [[Kandolf G]]  +
Has title [[File:Iyer.jpg|left|90px|Iyer Shilpa]] Bioenergetic profiling of patient derived human fibroblasts for mitochondrial diseases. [[Media:Shilpa_MIPConference_CR_forweb2017.pdf|Iyer_Presentation]]  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Respiration  + , mtDNA;mt-genetics  + , Patients  +
Stress Mitochondrial disease  +
Tissue and cell Fibroblast  +
Was published by MiPNetLab US AR Fayetteville Iyer S +
Was submitted in year 2017  +
Was submitted to event MiP2017/MitoEAGLE Hradec Kralove CZ +
Was written by Dhamad A + , Bakare A + , Iyer S +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
15:43:34, 4 December 2017  +
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