The Use of Skin Fibroblast Cultures in the Detection of Respiratory Chain Defects in Patients with Lacticacidemia

Robinson, Barry; Dm, Glerum; Chow, Wendy; Petrova‐Benedict, Roumyana; Lightowlers, Robert N.; Capaldi, Roderick A.

doi:10.1203/00006450-199011000-00027

Cited by 93 publications

(45 citation statements)

References 16 publications

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“…Statistical analysis of the results was performed with a paired t test. Spectrophotometric measurements of respiratory chain enzyme activities were carried out as reported (17).…”

Section: Methodsmentioning

confidence: 99%

Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport

Ferreirinha¹,

Quattrini²,

Pirozzi³

et al. 2004

J. Clin. Invest.

128

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“…Statistical analysis of the results was performed with a paired t test. Spectrophotometric measurements of respiratory chain enzyme activities were carried out as reported (17).…”

Section: Methodsmentioning

confidence: 99%

Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport

Ferreirinha¹,

Quattrini²,

Pirozzi³

et al. 2004

J. Clin. Invest.

128

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“…This contrasts sharply with a muscle biopsy, which is an invasive procedure that requires sedation, if not general anesthesia. Fibroblasts have a long tract record of utility in the study of mitochondrial disease biochemistry [108]. Added benefits of cultured skin fibroblasts are that they can be stored indefinitely, used as a renewable source of DNA, and recultured for testing as new tests become available [109,110].…”

Section: Fibroblast Analysismentioning

confidence: 99%

The in-depth evaluation of suspected mitochondrial disease

Haas

Parikh

Falk

et al. 2008

Molecular Genetics and Metabolism

313

300

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Mitochondrial disease confirmation and establishment of a specific molecular diagnosis requires extensive clinical and laboratory evaluation. Dual genome origins of mitochondrial disease, multiorgan system manifestations, and an ever increasing spectrum of recognized phenotypes represent the main diagnostic challenges. To overcome these obstacles, compiling information from a variety of diagnostic laboratory modalities can often provide sufficient evidence to establish an etiology. These include blood and tissue histochemical and analyte measurements, neuroimaging, provocative testing, enzymatic assays of tissue samples and cultured cells, as well as DNA analysis. As interpretation of results from these multifaceted investigations can become quite complex, the Diagnostic Committee of the Mitochondrial Medicine Society developed this review to provide an overview of currently available and emerging methodologies for the diagnosis of primary mitochondrial disease, primarily focusing on disorders characterized by impairment of oxidative phosphorylation. The aim of this work is to facilitate the diagnosis of mitochondrial disease by geneticists, neurologists, and other metabolic specialists who face the challenge of evaluating patients of all ages with suspected mitochondrial disease.

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“…Mitochondria were isolated from cultured skin fibroblasts (8) and the activity of the rotenone-sensitive NADH-cytochrome c reductase (complexes I ϩ III) was measured by the method of Moreadith et al (9). Activities of the other respiratory chain components were measured from whole cell extracts as follows: cytochrome oxidase (complex IV) by the method of DiMauro et al (10), and succinate cytochrome c reductase by following the reduction of cytochrome c (complexes II ϩ III) by the method of Fischer et al (11).…”

Section: Patients) By Mild Symptoms (Ms)mentioning

confidence: 99%

Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.

Pitkänen¹,

Robinson²

1996

J. Clin. Invest.

364

202

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Mitochondria were isolated from skin fibroblast cultures derived from healthy individuals (controls) and from a group patients with complex I (NADH-CoQ reductase) deficiency of the mitochondrial respiratory chain. The complex I deficient patients included those with fatal infantile lactic acidosis (FILA), cardiomyopathy with cataracts (CC), hepatopathy with tubulopathy (HT), Leigh's disease (LD), cataracts and developmental delay (CD), and lactic acidemia in the neonatal period followed by mild symptoms (MS). Production of superoxide radicals, on addition of NADH, were measured using the luminometric probe lucigenin with isolated fibroblast mitochondrial membranes. Superoxide production rates were highest with CD and decreased in the order CD ϾϾ MS Ͼ LD Ͼ control Ͼ HT Ͼ FILA ϭ CC. The quantity of Mn-superoxide dismutase (MnSOD), as measured by ELISA techniques, however, was highest in CC and FILA and lowest in CD. Plots of MnSOD quantity versus superoxide production showed an inverse relationship for most conditions with complex I deficiency. We hypothesize that oxygen radical production is increased when complex I activity is compromised. However, the ob-

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The Use of Skin Fibroblast Cultures in the Detection of Respiratory Chain Defects in Patients with Lacticacidemia

Cited by 93 publications

References 16 publications

Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport

Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport

The in-depth evaluation of suspected mitochondrial disease

Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.

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