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Article
Open AccessMetabolic impact of genetic and chemical ADP/ATP carrier inhibition in renal proximal tubule epithelial cells
Mitochondrial dysfunction is pivotal in drug-induced acute kidney injury (AKI), but the underlying mechanisms remain largely unknown. Transport proteins embedded in the mitochondrial inner membrane form a sign...
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Disorders of Mitochondrial Carriers
Most mitochondrial metabolic pathways are heavily interconnected and dependent on cytosolic metabolic routes. To allow such a cooperative action, a large variety of metabolites need to be exchanged between bot...
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Disorders of Mitochondrial Homeostasis, Dynamics, Protein Import, and Quality Control
This chapter describes gene mutations and disorders linked to mitochondrial homeostasis, dynamics, protein import, and quality control. Although clinically highly variable, we here functionally categorized the...
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Article
Open AccessNatural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study
SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dy...
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Article
Open AccessCorrection to: The antioxidant Trolox restores mitochondrial membrane potential and Ca2+-stimulated ATP production in human complex I deficiency
A Correction to this paper has been published: https://doi.org/10.1007/s00109-021-02057-3
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Article
Open AccessThe Redox Modulating Sonlicromanol Active Metabolite KH176m and the Antioxidant MPG Protect Against Short-Duration Cardiac Ischemia-Reperfusion Injury
Sonlicromanol is a phase IIB clinical stage compound developed for treatment of mitochondrial diseases. Its active component, KH176m, functions as an antioxidant, directly scavenging reactive oxygen species (R...
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Article
One mutation, three phenotypes: novel metabolic insights on MELAS, MIDD and myopathy caused by the m.3243A > G mutation
The m.3243A > G mitochondrial DNA mutation is one of the most common mitochondrial disease-causing mutations, with a carrier rate as high as 1:400. This point mutation affects the MT-TL1 gene, ultimately affec...
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Article
Open AccessDelineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population
Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genet...
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Article
Open AccessPsychological functioning in children suspected for mitochondrial disease: the need for care
Mitochondrial diseases (MD) are generally serious and progressive, inherited metabolic diseases. There is a high comorbidity of anxiety and depression and limitations in daily functioning. The complexity and d...
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Article
Open AccessRescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD+
Cell models of mitochondrial complex I (CI) deficiency display activation of glycolysis to compensate for the loss in mitochondrial ATP production. This adaptation can mask other relevant deficiency-induced ab...
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Article
Open AccessKH176 Safeguards Mitochondrial Diseased Cells from Redox Stress-Induced Cell Death by Interacting with the Thioredoxin System/Peroxiredoxin Enzyme Machinery
A deficient activity of one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzyme complexes leads to devastating diseases, with high unmet medical needs. Mitochondria, and more specifically th...
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Domains of Daily Physical Activity in Children with Mitochondrial Disease: A 3D Accelerometry Approach
Feasible, sensitive and clinically relevant outcome measures are of extreme importance when designing clinical trials. For paediatric mitochondrial disease, no robust end point has been described to date. The ...
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Article
Multiplexed high-content analysis of mitochondrial morphofunction using live-cell microscopy
This protocol describes a high-content microscopy approach to quantifying mitochondrial morphofunction in living cells. After staining with fluorescent reporters, images are automatically acquired, processed a...
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Article
Open AccessInternational Paediatric Mitochondrial Disease Scale
There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochon...
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Article
Open AccessMitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity
Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R ...
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Article
High prevalence of complementary and alternative medicine use in patients with genetically proven mitochondrial disorders
Despite major advances in understanding the pathophysiology of mitochondrial diseases, clinical management of these conditions remains largely supportive, and no effective treatment is available. We therefore ...
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Article
Treatment options for lactic acidosis and metabolic crisis in children with mitochondrial disease
The mitochondrial pyruvate oxidation route is a tightly regulated process, which is essential for aerobic cellular energy production. Disruption of this pathway may lead to severe neurometabolic disorders with...
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Article
Open AccessQuantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning
In primary fibroblasts from Leigh Syndrome (LS) patients, isolated mitochondrial complex I deficiency is associated with increased reactive oxygen species levels and mitochondrial morpho-functional changes. Em...
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Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers
In this observational cohort study, we examined the prognostic value of growth and differentiation factor 15 (GDF15) in indicating and monitoring general mitochondrial disease severity and progression in adult...
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Article
3-Methylglutaconic aciduria—lessons from 50 genes and 977 patients
Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine d...
