Diagnosis of mitochondrial disorders: Clinical and biochemical approach

2001 ◽  
Vol 24 (2) ◽  
pp. 312-316 ◽  
Author(s):  
D. R. Thorburn ◽  
J. Smeitink
Keyword(s):  
Mitochondrial Disorders ◽  
Biochemical Approach

Primary mitochondrial disorders and diabetes mellitus - two case reports

2018 ◽  
Author(s):  
Lucia Fadiga ◽  
Joana Saraiva ◽  
Diana Oliveira ◽  
Adriana Lages ◽  
Mara Ventura ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Case Reports ◽  
Mitochondrial Disorders

scholarly journals Activation of NF-κB signaling via cytosolic mitochondrial RNA sensing in kerotocytes with mitochondrial DNA common deletion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Zhou ◽  
Ludvig J. Backman ◽  
Patrik Danielson
Keyword(s):  
Wound Healing ◽  
Mitochondrial Dna ◽  
Scar Formation ◽  
Mitochondrial Rna ◽  
Peripheral Part ◽  
Double Stranded Rna ◽  
Corneal Wound ◽  
Biochemical Approach ◽  
Common Deletion ◽  
Underlying Mechanisms

AbstractScar formation as a result of corneal wound healing is a leading cause of blindness. It is a challenge to understand why scar formation is more likely to occur in the central part of the cornea as compared to the peripheral part. The purpose of this study was to unravel the underlying mechanisms. We applied RNA-seq to uncover the differences of expression profile in keratocytes in the central/peripheral part of the cornea. The relative quantity of mitochondrial RNA was measured by multiplex qPCR. The characterization of mitochondrial RNA in the cytoplasm was confirmed by immunofluoresence microscope and biochemical approach. Gene expression was analyzed by western blot and RT qPCR. We demonstrate that the occurrence of mitochondrial DNA common deletion is greater in keratocytes from the central cornea as compared to those of the peripheral part. The keratocytes with CD have elevated oxidative stress levels, which leads to the leakage of mitochondrial double-stranded RNA into the cytoplasm. The cytoplasmic mitochondrial double-stranded RNA is sensed by MDA5, which induces NF-κB activation. The NF-κB activation thereafter induces fibrosis-like extracellular matrix expressions and IL-8 mRNA transcription. These results provide a novel explanation of the different clinical outcome in different regions of the cornea during wound healing.

scholarly journals Global mapping of protein–metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Marcin Luzarowski ◽  
Rubén Vicente ◽  
Andrei Kiselev ◽  
Mateusz Wagner ◽  
Dennis Schlossarek ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Small Molecules ◽  
Phosphoglycerate Kinase ◽  
Glycolytic Enzyme ◽  
Diauxic Shift ◽  
Cellular Processes ◽  
Targeted Analysis ◽  
Global Mapping ◽  
Biochemical Approach ◽  
User Friendly

AbstractProtein–metabolite interactions are of crucial importance for all cellular processes but remain understudied. Here, we applied a biochemical approach named PROMIS, to address the complexity of the protein–small molecule interactome in the model yeast Saccharomyces cerevisiae. By doing so, we provide a unique dataset, which can be queried for interactions between 74 small molecules and 3982 proteins using a user-friendly interface available at https://promis.mpimp-golm.mpg.de/yeastpmi/. By interpolating PROMIS with the list of predicted protein–metabolite interactions, we provided experimental validation for 225 binding events. Remarkably, of the 74 small molecules co-eluting with proteins, 36 were proteogenic dipeptides. Targeted analysis of a representative dipeptide, Ser-Leu, revealed numerous protein interactors comprising chaperones, proteasomal subunits, and metabolic enzymes. We could further demonstrate that Ser-Leu binding increases activity of a glycolytic enzyme phosphoglycerate kinase (Pgk1). Consistent with the binding analysis, Ser-Leu supplementation leads to the acute metabolic changes and delays timing of a diauxic shift. Supported by the dipeptide accumulation analysis our work attests to the role of Ser-Leu as a metabolic regulator at the interface of protein degradation and central metabolism.

scholarly journals Serum biomarkers in primary mitochondrial disorders

2021 ◽  
Author(s):  
Kristin N Varhaug ◽  
Omar Hikmat ◽  
Hanne Linda Nakkestad ◽  
Christian A Vedeler ◽  
Laurence A Bindoff
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mitochondrial Disease ◽  
Central Nervous System Involvement ◽  
Mitochondrial Disorders ◽  
Serum Biomarkers ◽  
Fibroblast Growth Factor 21 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mitochondrial Dna Deletion ◽  
Muscle Involvement

Abstract The aim of this study was to explore the utility of the serum biomarkers neurofilament light chain (NF-L), fibroblast growth factor 21 (FGF-21) and growth and differentiation factor 15 (GDF-15) in diagnosing primary mitochondrial disorders. We measured serum NF-L, FGF-21 and GDF-15 in 26 patients with a genetically proven mitochondrial disease. FGF-21 and GDF-15 were measured by enzyme-linked immunosorbent assay and NF-L with the Simoa assay. NF-L was highest in patients with multisystemic involvement that included the central nervous system such as those with the m.3242A>G mutation. Mean NF-L was also highest in patients with epilepsy versus those without (49.74 pg/ml versus 19.7 pg/ml (p = 0.015)), while FGF-21 and GDF-15 levels were highest in patients with prominent myopathy, such as those with single mitochondrial DNA deletion. Our results suggest that the combination of NF-L, FGF-21 and GDF-15 is useful in the diagnostic evaluation of mitochondrial disease. GDF-15 and FGF-21 identify those with muscle involvement while NF-L is a clear marker for central nervous system involvement independent of underlying mitochondrial pathology. Levels of NF-L appear to correlate with the degree of ongoing damage suggesting, therefore, that monitoring NF-L levels may provide prognostic information and a way of monitoring disease activity.

scholarly journals Mitochondrial Syndromes Revisited

2021 ◽  
Vol 10 (6) ◽  
pp. 1249
Author(s):  
Daniele Orsucci ◽  
Elena Caldarazzo Ienco ◽  
Andrea Rossi ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Clinical Trials ◽  
Genetic Basis ◽  
Phenotypic Variability ◽  
Mitochondrial Diseases ◽  
Genetic Alterations ◽  
Mitochondrial Disorders ◽  
Single Mutation ◽  
Multicenter Studies ◽  
Future Studies ◽  
Clinical Syndromes

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

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