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Open AccessArticle

Global Proteome of LonP1+/− Mouse Embryonal Fibroblasts Reveals Impact on Respiratory Chain, but No Interdependence between Eral1 and Mitoribosomes

1
Experimental Neurology, Goethe University Medical School, 60590 Frankfurt am Main, Germany
2
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain
3
Functional Proteomics Group, Goethe-University Hospital, 60590 Frankfurt am Main, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4523; https://doi.org/10.3390/ijms20184523
Received: 9 July 2019 / Revised: 2 September 2019 / Accepted: 9 September 2019 / Published: 12 September 2019
(This article belongs to the Special Issue Rhine-Main Neuroscience Network: rmn^2-Oberwesel 2018)
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+/− mouse embryonal fibroblasts (MEF), for comparison with ClpP−/− depletion. Proteomic profiles of LonP1+/− 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+/− MEF also showed Eral1 accumulation, but no systematic effect on mitoribosomal subunits. In contrast to ClpP−/− 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. View Full-Text
Keywords: longevity; life expectancy; CODAS syndrome; Perrault syndrome; protease target substrates; respiratory complex assembly; oxidative stress; glutathione pathway; lysosomal degradation; fidelity protein synthesis longevity; life expectancy; CODAS syndrome; Perrault syndrome; protease target substrates; respiratory complex assembly; oxidative stress; glutathione pathway; lysosomal degradation; fidelity protein synthesis
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Key, J.; Kohli, A.; Bárcena, C.; López-Otín, C.; Heidler, J.; Wittig, I.; Auburger, G. Global Proteome of LonP1+/− Mouse Embryonal Fibroblasts Reveals Impact on Respiratory Chain, but No Interdependence between Eral1 and Mitoribosomes. Int. J. Mol. Sci. 2019, 20, 4523.

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