دورية أكاديمية
Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA
| العنوان: | Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA |
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| المؤلفون: | Jana Key, Sylvia Torres-Odio, Nina C. Bach, Suzana Gispert, Gabriele Koepf, Marina Reichlmeir, A. Phillip West, Holger Prokisch, Peter Freisinger, William G. Newman, Stavit Shalev, Stephan A. Sieber, Ilka Wittig, Georg Auburger |
| المصدر: | Cells, Vol 10, Iss 12, p 3354 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | leukodystrophy, ataxia, Parkinson’s disease, HARS2, LARS2, TWNK, Cytology, QH573-671 |
| الوصف: | Biallelic pathogenic variants in CLPP, encoding mitochondrial matrix peptidase ClpP, cause a rare autosomal recessive condition, Perrault syndrome type 3 (PRLTS3). It is characterized by primary ovarian insufficiency and early sensorineural hearing loss, often associated with progressive neurological deficits. Mouse models showed that accumulations of (i) its main protein interactor, the substrate-selecting AAA+ ATPase ClpX, (ii) mitoribosomes, and (iii) mtDNA nucleoids are the main cellular consequences of ClpP absence. However, the sequence of these events and their validity in human remain unclear. Here, we studied global proteome profiles to define ClpP substrates among mitochondrial ClpX interactors, which accumulated consistently in ClpP-null mouse embryonal fibroblasts and brains. Validation work included novel ClpP-mutant patient fibroblast proteomics. ClpX co-accumulated in mitochondria with the nucleoid component POLDIP2, the mitochondrial poly(A) mRNA granule element LRPPRC, and tRNA processing factor GFM1 (in mouse, also GRSF1). Only in mouse did accumulated ClpX, GFM1, and GRSF1 appear in nuclear fractions. Mitoribosomal accumulation was minor. Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely, OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2, and ACADSB, but the impact on downstream metabolites was marginal. Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids and show nucleoid enlargement in human as a key consequence. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2073-4409 39217604 |
| العلاقة: | https://www.mdpi.com/2073-4409/10/12/3354Test; https://doaj.org/toc/2073-4409Test |
| DOI: | 10.3390/cells10123354 |
| الوصول الحر: | https://doaj.org/article/392176045a06439686ba95e970055680Test |
| رقم الانضمام: | edsdoj.392176045a06439686ba95e970055680 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20734409 39217604 |
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| DOI: | 10.3390/cells10123354 |