Nutritional and exercise-based therapies in the treatment of mitochondrial disease

Mahoney, Douglas J.; Parise, Gianni; Tarnopolsky, Mark A.

doi:10.1097/00075197-200211000-00004

Cited by 56 publications

(41 citation statements)

References 91 publications

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“…Endurance training increases capillarization of muscle and the density of mitochondria in individual cells, whereas resistance training recruits satellite muscle cells into an active state of energy production. 66 In addition, a variety of drugs and dietary supplements have been used in attempts to treat, or at least modulate the course of OXPHOS disorders. In a select group of patients deficient in coenzyme Q10, replacement of coenzyme Q10 or its synthetic analogue idebenone can restore electron flow in the respiratory chain.…”

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

“…For complex I deficiency, bypass of this complex has been tried using electron transfer mediators such as succinate and triacylglycerol, or a high fat and low carbohydrate diet. 66 Supplement of nicotinamide has been theorized to provide increased NADH for complex I, and vitamin precursors or cofactors (e.g., riboflavin, thiamin, niacin, and vitamin K) may boost production of certain complexes of the respiratory chain. 66,68 Antioxidant use (e.g., vitamin C, vitamin E, or lipoic acid) remains popular to scavenge the free radicals that accumulate in patients with OX-PHOS disorders.…”

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

“…66 Supplement of nicotinamide has been theorized to provide increased NADH for complex I, and vitamin precursors or cofactors (e.g., riboflavin, thiamin, niacin, and vitamin K) may boost production of certain complexes of the respiratory chain. 66,68 Antioxidant use (e.g., vitamin C, vitamin E, or lipoic acid) remains popular to scavenge the free radicals that accumulate in patients with OX-PHOS disorders. 68 Carnitine has long been used, as patients with OXPHOS disorders may be secondarily deficient in carnitine, in an attempt to prevent toxicity of acyl-coenzyme A.…”

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

“…68 Carnitine has long been used, as patients with OXPHOS disorders may be secondarily deficient in carnitine, in an attempt to prevent toxicity of acyl-coenzyme A. 66 Newer treatments include creatine monohydrate (potential alternative energy source of phosphocreatine), L-arginine (a vasodilator which may prevent stroke-like episodes inpatients with MELAS), and uridine (to replace a putative pyrimidine deficiency inpatients with oxidative phosphorylation disorders). 66 …”

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

“…66 Newer treatments include creatine monohydrate (potential alternative energy source of phosphocreatine), L-arginine (a vasodilator which may prevent stroke-like episodes inpatients with MELAS), and uridine (to replace a putative pyrimidine deficiency inpatients with oxidative phosphorylation disorders). 66 …”

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

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Mitochondrial ribosomal proteins: Candidate genes for mitochondrial disease

Sylvester

Fischel‐Ghodsian

Mougey

et al. 2004

Genetics in Medicine

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Most of the energy requirement for cell growth, differentiation, and development is met by the mitochondria in the form of ATP produced by the process of oxidative phosphorylation. Human mitochondrial DNA encodes a total of 13 proteins, all of which are essential for oxidative phosphorylation. The mRNAs for these proteins are translated on mitochondrial ribosomes. Recently, the genes for human mitochondrial ribosomal proteins (MRPs) have been identified. In this review, we summarize their refined chromosomal location. It is well known that mutations in the mitochondrial translation system, i.e., ribosomal RNA and transfer RNA cause various pathologies. In this review, we suggest possible associations between clinical conditions and MRPs based on coincidence of genetic map data and chromosomal location. These MRPs may be candidate genes for the clinical condition or may act as modifiers of existing known gene mutations (mt-tRNA, mt-rRNA, etc.). Genet Med 2004:6(2):73-80.

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Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

Section: Therapies For Oxidative Phosphorylation Disordersmentioning

confidence: 99%

See 3 more Smart Citations

Mitochondrial ribosomal proteins: Candidate genes for mitochondrial disease

Sylvester

Fischel‐Ghodsian

Mougey

et al. 2004

Genetics in Medicine

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Complex II deficiency—A case report and review of the literature

Jain-Ghai

Cameron

Maawali

et al. 2013

American J of Med Genetics Pt A

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Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23%. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB are catalytic and SDHC and SDHD are anchoring. Mutations in SDHA and SDHAF1 (assembly factor) have been found in patients with CII deficiency and a mitochondrial phenotype. We present a patient with CII deficiency with a previously undescribed phenotype of dilated cardiomyopathy, left ventricular noncompaction, failure to thrive, hypotonia, and developmental delay. Also, a comprehensive review of 36 cases published in the literature was undertaken. The results show that CII deficiency has a variable phenotype with no correlation with residual complex activity in muscle although the phenotype and enzyme activities are comparable within a family. For some, the condition was fatal in infancy, others had multisystem involvement and some had onset in adulthood with mild symptoms and normal cognition. Neurological involvement is most commonly observed and brain imaging commonly shows leukoencephalopathy, Leigh syndrome, or cerebellar atrophy. Mutations in SDHAF1 are associated with leukoencephalopathy. Other organ systems like heart, muscle, and eyes are only involved in about 50% of the cases but cardiomyopathy is associated with high mortality and morbidity. In some patients, riboflavin has provided clinical improvement.

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Bezafibrate induced increase in mitochondrial electron transport chain complex IV activity in human astrocytoma cells: Implications for mitochondrial cytopathies and neurodegenerative diseases

et al. 2010

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Mitochondrial encephalomyopathies resulting from electron transport chain (ETC) dysfunction can present with a wide spectrum of clinical manifestations having significant neuropathology and a progressive nature. Despite advances in diagnosis of ETC disorders, treatment still remains inadequate. A recent study in fibroblasts and myoblasts revealed the ability of fibrate treatment to correct ETC enzyme deficiencies. Therefore, fibrates may represent potential therapeutic agents to correct the neurological ETC impairment responsible for the encephalopathic presentation of these disorders. Consequently, this study assessed the effect of bezafibrate on human astrocytoma (HA) 1321N cell ETC activity and coenzyme Q(10) (CoQ(10) ) status. HA cells were incubated for 72 H with 300 μM or 500 μM bezafibrate and for 7 days with only 500 μM bezafibrate. A significant effect on ETC activity was observed after 7 days incubation with 500 μM bezafibrate yielding a 130% (P < 0.05) increase in complex IV activity, accompanied by a 33% (P < 0.05) increase in cellular ATP level and a 25% (P < 0.001) decrease in extracellular lactate/pyruvate ratio compared to control levels. Following 7 days culture with bezafibrate, the CoQ(10) status of the HA cells appeared to increase although this was not found to be significant. The results of this study have indicated evidence of a bezafibrate induced increase in ETC complex IV activity. Further studies are required to assess the ability of bezafibrate treatment to correct neurological ETC impairment in available animal models of ETC dysfunction before the therapeutic efficacy of this pharmacological agent can be further considered in the treatment of the encephalopathic presentation of ETC disorders.

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Nutritional and exercise-based therapies in the treatment of mitochondrial disease

Cited by 56 publications

References 91 publications

Mitochondrial ribosomal proteins: Candidate genes for mitochondrial disease

Mitochondrial ribosomal proteins: Candidate genes for mitochondrial disease

Complex II deficiency—A case report and review of the literature

Bezafibrate induced increase in mitochondrial electron transport chain complex IV activity in human astrocytoma cells: Implications for mitochondrial cytopathies and neurodegenerative diseases

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