Progressive myopathy with a combined respiratory chain defect including Complex II

Rodrigues, Andresa De Santi; Kiyomoto, Beatriz Hitomi; Oliveira, Acary Souza Bullé; Gabbai, Alberto Alain; Schmidt, Beny; Tengan, Célia Harumi

doi:10.1016/j.jns.2007.08.002

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…They could not be included in the previous quantitative analysis due to the absence of normal fibres (patient 30) or normal pattern of SDH and COX staining (patient 31). Muscle biopsy of patient 30 showed a diffuse complex II deficiency, RRF/COX+ fibres, scattered COX− fibres and a Complex I deficiency, as reported previously 36 . Although the genetic defect is unknown, the unique feature of diffuse SDH deficiency allowed us to verify whether SDH activity could have any effect on NADPHd activity.…”

Section: Resultssupporting

confidence: 84%

Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

Rodrigues

Godinho

Kiyomoto

et al. 2016

Sci Rep

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Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events.

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Section: Resultssupporting

confidence: 84%

Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

Rodrigues

Godinho

Kiyomoto

et al. 2016

Sci Rep

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“…However, in addition to the profound SDH defects evidenced in phaeochromocytomas and paragangliomas or gastrointestinal stromal tumor tissues of patients with germline mutations in the SDH tumor suppressor genes [47–50], a partial SDH deficiency has been observed in a number of human diseases that affect one or several organs, i . e ., FRDA [51], Barth syndrome [52], various leukoencephalopathies [53] [54] [55], asthenozoospermia male infertility [56], myopathy [57], rare hemolytic uremic syndromes and rhabdomyolysis [58]. This feature defines a subpopulation that might be particularly at risk when in contact with SDHIs.…”

Section: Discussionmentioning

confidence: 99%

Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells

et al. 2019

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Succinate dehydrogenase (SDH) inhibitors (SDHIs) are used worldwide to limit the proliferation of molds on plants and plant products. However, as SDH, also known as respiratory chain (RC) complex II, is a universal component of mitochondria from living organisms, highly conserved through evolution, the specificity of these inhibitors toward fungi warrants investigation. We first establish that the human, honeybee, earthworm and fungal SDHs are all sensitive to the eight SDHIs tested, albeit with varying IC50 values, generally in the micromolar range. In addition to SDH, we observed that five of the SDHIs, mostly from the latest generation, inhibit the activity of RC complex III. Finally, we show that the provision of glucose ad libitum in the cell culture medium, while simultaneously providing sufficient ATP and reducing power for antioxidant enzymes through glycolysis, allows the growth of RC-deficient cells, fully masking the deleterious effect of SDHIs. As a result, when glutamine is the major carbon source, the presence of SDHIs leads to time-dependent cell death. This process is significantly accelerated in fibroblasts derived from patients with neurological or neurodegenerative diseases due to RC impairment (encephalopathy originating from a partial SDH defect) and/or hypersensitivity to oxidative insults (Friedreich ataxia, familial Alzheimer’s disease).

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2008

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Progressive myopathy with a combined respiratory chain defect including Complex II

Cited by 3 publications

References 23 publications

Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells

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