Global proteome of LonP1+/- mouse embryonal fibroblasts reveals impact on respiratory chain, but no interdependence between eral1 and mitoribosomes
| Autor: | Jana Key, Georg Auburger, Ilka Wittig, Clea Bárcena, Aneesha Kohli, Carlos López-Otín, Juliana Heidler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
CODAS syndrome
Proteome Protein subunit Respiratory chain Catalysis Article Inorganic Chemistry Electron Transport Mitochondrial Proteins Mitochondrial Ribosomes fidelity protein synthesis lcsh:Chemistry Mice respiratory complex assembly glutathione pathway Downregulation and upregulation ATP-Dependent Proteases longevity GTP-Binding Proteins Animals oxidative stress biochemistry Protein Interaction Maps Physical and Theoretical Chemistry Molecular Biology Gene lcsh:QH301-705.5 Spectroscopy Cells Cultured protease target substrates Innate immune system Perrault syndrome biology Chemistry Organic Chemistry RNA-Binding Proteins General Medicine Fibroblasts Embryo Mammalian Computer Science Applications Cell biology lysosomal degradation lcsh:Biology (General) lcsh:QD1-999 Mitochondrial matrix Chaperone (protein) biology.protein life expectancy |
| Zdroj: | Scopus International Journal of Molecular Sciences, Vol 20, Iss 18, p 4523 (2019) RUO. Repositorio Institucional de la Universidad de Oviedo instname International Journal of Molecular Sciences Volume 20 Issue 18 |
| Popis: | Research on healthy aging shows that lifespan reductions are often caused by mitochondrial dysfunction. Thus, it is very interesting that the deletion of mitochondrial matrix peptidase LonP1 was observed to abolish embryogenesis, while deletion of the mitochondrial matrix peptidase Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit (ClpP) prolonged survival. To unveil the targets of each enzyme, we documented the global proteome of LonP1+/&minus mouse embryonal fibroblasts (MEF), for comparison with ClpP&minus /&minus depletion. Proteomic profiles of LonP1+/&minus MEF generated by label-free mass spectrometry were further processed with the STRING (Search tool for the retrieval of interacting genes) webserver Heidelberg for protein interactions. ClpP was previously reported to degrade Eral1 as a chaperone involved in mitoribosome assembly, so ClpP deficiency triggers the accumulation of mitoribosomal subunits and inefficient translation. LonP1+/&minus MEF also showed Eral1 accumulation, but no systematic effect on mitoribosomal subunits. In contrast to ClpP&minus profiles, several components of the respiratory complex-I membrane arm, of the glutathione pathway and of lysosomes were accumulated, whereas the upregulation of numerous innate immune defense components was similar. Overall, LonP1, as opposed to ClpP, appears to have no effect on translational machinery, instead it shows enhanced respiratory dysfunction this agrees with reports on the human CODAS syndrome (syndrome with cerebral, ocular, dental, auricular, and skeletal anomalies) caused by LonP1 mutations. |
| Databáze: | OpenAIRE |
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