ABSTRACT
BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %), thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Ataxia/genetics , Electron Transport/genetics , Mutation , Mitochondrial Diseases/genetics , Muscle Weakness/genetics , Ubiquinone/analogs & derivatives , Ubiquinone/deficiency , Ataxia/diagnosis , Ataxia/metabolism , Biopsy , Cells, Cultured , Chromatography, Liquid , Fibroblasts/enzymology , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/metabolism , Muscle Weakness/diagnosis , Muscle Weakness/metabolism , Muscles/pathology , Spectrophotometry/methods , Tandem Mass Spectrometry/methods , Ubiquinone/biosynthesis , Ubiquinone/genetics , Ubiquinone/metabolismABSTRACT
Introduction: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. Methodology: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. Results: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. Conclusions: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects. .
Subject(s)
Humans , Central Nervous System/physiopathology , Mental Disorders/physiopathology , Mitochondria/physiology , Mitochondrial Diseases/physiopathology , Apoptosis/physiology , Central Nervous System/metabolism , Energy Metabolism , Mental Disorders/etiology , Mental Disorders/metabolism , Mitochondria/drug effects , Mitochondrial Diseases/metabolismABSTRACT
It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (DM2) and its chronic complications, and that genetically susceptible subjects can develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2. Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism. All these mechanisms are associated with DM2 pathogenesis and its chronic complications. Therefore, UCP2 is a candidate gene for the development of these disorders. Indeed, several studies have reported that three common polymorphisms in UCP2 gene are possibly associated with DM2 and/or obesity. Only a few studies investigated these polymorphisms in relation to chronic complications of diabetes, with inconclusive results.
Está bem estabelecido que fatores genéticos têm papel importante no desenvolvimento do diabetes melito tipo 2 (DM2) bem como de suas complicações crônicas e que indivíduos geneticamente suscetíveis podem desenvolver essa doença após exposição a fatores de risco ambientais. Assim, grandes esforços têm sido feitos para a identificação de genes associados ao DM2. A proteína desacopladora 2 (UCP2) é expressa em diversos tecidos e atua na proteção contra o estresse oxidativo, na regulação negativa da secreção de insulina pelas células-beta e no metabolismo dos ácidos graxos, mecanismos associados tanto à patogênese do DM2 como a suas complicações crônicas. Portanto, o gene UCP2 é um gene candidato para o desenvolvimento dessas doenças. De fato, diversos estudos têm relatado que três polimorfismos comuns no gene UCP2 estão possivelmente associados ao DM2 e/ou à obesidade. Apenas poucos estudos investigaram esses polimorfismos em relação às complicações crônicas do diabetes, obtendo resultados pouco conclusivos.