Publications by authors named "J N Spelbrink"
Article Synopsis
- * Research identified two genetic variants (P114T and L128V) in patients suspected of mitochondrial disease, which result in less stable SIRT5 protein and lower activity without creating new harmful effects.
- * A mouse model mimicking the P114T mutation demonstrates reduced SIRT5 levels, but does not show significant metabolic or neurological issues, suggesting that these genetic variants alone are unlikely to be the main cause of the neurological problems in patients.
Article Synopsis
- SIRT5 is a deacylase involved in removing negatively-charged lysine modifications, mostly active in the mitochondrial matrix.
- Two specific variants in SIRT5 (P114T and L128V) found in human patients with severe mitochondrial disease lead to decreased protein stability and activity, but do not show signs of dominant negative effects.
- A mouse model created to mimic the P114T variant shows reduced SIRT5 levels and activity without significant health issues, suggesting the variants might not be the main cause of the patients' neurological symptoms.
Complexome profiling (CP) is a powerful tool for systematic investigation of protein interactors that has been primarily applied to study the composition and dynamics of mitochondrial protein complexes. Here, we further optimized this method to extend its application to survey mitochondrial DNA- and RNA-interacting protein complexes. We established that high-resolution clear native gel electrophoresis (hrCNE) is a better alternative to preserve DNA- and RNA-protein interactions that are otherwise disrupted when samples are separated by the widely used blue native gel electrophoresis (BNE).
View Article and Find Full Text PDFMolecular functions of many human proteins remain unstudied, despite the demonstrated association with diseases or pivotal molecular structures, such as mitochondrial DNA (mtDNA). This small genome is crucial for the proper functioning of mitochondria, the energy-converting organelles. In mammals, mtDNA is arranged into macromolecular complexes called nucleoids that serve as functional stations for its maintenance and expression.
View Article and Find Full Text PDFMitochondrial DNA has been investigated for nearly fifty years, but many aspects of the maintenance of this essential small genome remain unknown. Like any genome, mammalian mitochondrial DNA requires the function of topoisomerases to counter and regulate the topological tension arising during replication, transcription, segregation, and repair. However, the functions of the different mitochondrial topoisomerases are poorly understood.
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