Publications by authors named "Melissa van de Wal"
Ndufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response.
Biochim Biophys Acta Proteins Proteom
January 2025
Article Synopsis
- Paediatric Leigh syndrome (LS) is a severe neurodegenerative disorder caused by mutations in the NDUFS4 gene, which affects mitochondrial function, and currently has no effective treatments.
- Researchers used whole-body Ndufs4 knockout (KO) mice to analyze differences in brain proteomes between these mice and wildtype mice, identifying variations across different brain regions.
- Findings highlighted reduced levels of critical mitochondrial components in specific brain areas and suggested that attempts to stimulate certain metabolic pathways could be harmful, prompting the need for new therapeutic strategies for managing LS.
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 significant class of potential drug off-targets. So far, most transporter-drug interactions have been reported for the mitochondrial ADP/ATP carrier (AAC).
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- This study investigates how short-chain fatty acids (SCFAs), specifically butyrate, affect magnesium (Mg) absorption in the intestines and its relationship with gut bacteria.
- Researchers found that higher butyrate levels in the colon correlate with lower serum magnesium levels in mice.
- The study reveals that butyrate inhibits Mg absorption by directly affecting a specific channel in gut cells, indicating that butyrate's influence on mineral absorption is independent of metabolic changes.
Attachment of cargo molecules to lipophilic triphenylphosphonium (TPP) cations is a widely applied strategy for mitochondrial targeting. We previously demonstrated that the vitamin E-derived antioxidant Trolox increases the levels of active mitochondrial complex I (CI), the first complex of the electron transport chain (ETC), in primary human skin fibroblasts (PHSFs) of Leigh Syndrome (LS) patients with isolated CI deficiency. Primed by this finding, we here studied the cellular effects of mitochondria-targeted Trolox (MitoE10), mitochondria-targeted ubiquinone (MitoQ10) and their mitochondria-targeting moiety decylTPP (C-TPP).
View Article and Find Full Text PDFMitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial diseases. With respect to the latter, mutations in subunit-encoding genes and assembly factors of the first OXPHOS complex (complex I) induce isolated complex I deficiency and Leigh syndrome.
View Article and Find Full Text PDFThe ketogenic diet as a therapeutic intervention strategy in mitochondrial disease.
Int J Biochem Cell Biol
September 2021
Classical mitochondrial disease (MD) represents a group of complex metabolic syndromes primarily linked to dysfunction of the mitochondrial ATP-generating oxidative phosphorylation (OXPHOS) system. To date, effective therapies for these diseases are lacking. Here we discuss the ketogenic diet (KD), being a high-fat, moderate protein, and low carbohydrate diet, as a potential intervention strategy.
View Article and Find Full Text PDFMitochondrial complex I (CI), the first multiprotein enzyme complex of the OXPHOS system, executes a major role in cellular ATP generation. Consequently, dysfunction of this complex has been linked to inherited metabolic disorders, including Leigh disease (LD), an often fatal disease in early life. Development of clinical effective treatments for LD remains challenging due to the complex pathophysiological nature.
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- The ability to manage social interactions hinges on effectively integrating social and environmental cues; failure to do so can lead to issues like aggression and social withdrawal, often seen in conditions like conduct disorder and autism spectrum disorder.
- Research indicates that structural changes in the anterior and midcingulate cortices are linked to these behavioral issues, but the precise nature of these changes remains unclear.
- In a study with BALB/cJ mice, variations in the distribution of specific interneurons (parvalbumin and somatostatin) in the cingulate cortex were found to correlate with levels of aggression and social withdrawal, revealing distinct behavior patterns among more and less sociable mice.