| Autor: |
Auburger G; Experimental Neurology, Medical Faculty, Goethe University, 60590 Frankfurt am Main, Germany., Key J; Experimental Neurology, Medical Faculty, Goethe University, 60590 Frankfurt am Main, Germany., Gispert S; Experimental Neurology, Medical Faculty, Goethe University, 60590 Frankfurt am Main, Germany. |
| Jazyk: |
angličtina |
| Zdroj: |
Cells [Cells] 2022 Aug 02; Vol. 11 (15). Date of Electronic Publication: 2022 Aug 02. |
| DOI: |
10.3390/cells11152370 |
| Abstrakt: |
In the matrix of bacteria/mitochondria/chloroplasts, Lon acts as the degradation machine for soluble proteins. In stress periods, however, proteostasis and survival depend on the strongly conserved Clp/Hsp100 family. Currently, the targets of ATP-powered unfoldases/disaggregases ClpB and ClpX and of peptidase ClpP heptameric rings are still unclear. Trapping experiments and proteome profiling in multiple organisms triggered confusion, so we analyzed the consistency of ClpP-trap targets in bacteria. We also provide meta-analyses of protein interactions in humans, to elucidate where Clp family members are enriched. Furthermore, meta-analyses of mouse complexomics are provided. Genotype-phenotype correlations confirmed our concept. Trapping, proteome, and complexome data retrieved consistent coaccumulation of CLPXP with GFM1 and TUFM orthologs. CLPX shows broad interaction selectivity encompassing mitochondrial translation elongation, RNA granules, and nucleoids. CLPB preferentially attaches to mitochondrial RNA granules and translation initiation components; CLPP is enriched with them all and associates with release/recycling factors. Mutations in CLPP cause Perrault syndrome, with phenotypes similar to defects in mtDNA/mtRNA. Thus, we propose that CLPB and CLPXP are crucial to counteract misfolded insoluble protein assemblies that contain nucleotides. This insight is relevant to improve ClpP-modulating drugs that block bacterial growth and for the treatment of human infertility, deafness, and neurodegeneration. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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