دورية أكاديمية
Global mitochondrial protein import proteomics reveal distinct regulation by translation and translocation machinery.
| العنوان: | Global mitochondrial protein import proteomics reveal distinct regulation by translation and translocation machinery. |
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| المؤلفون: | Schäfer JA; Institute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75, 60590 Frankfurt am Main, Germany., Bozkurt S; Institute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75, 60590 Frankfurt am Main, Germany., Michaelis JB; Institute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75, 60590 Frankfurt am Main, Germany., Klann K; Institute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75, 60590 Frankfurt am Main, Germany., Münch C; Institute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75, 60590 Frankfurt am Main, Germany; Frankfurt Cancer Institute, Frankfurt am Main, Germany; Cardio-Pulmonary Institute, Frankfurt am Main, Germany. Electronic address: ch.muench@em.uni-frankfurt.de. |
| المصدر: | Molecular cell [Mol Cell] 2022 Jan 20; Vol. 82 (2), pp. 435-446.e7. Date of Electronic Publication: 2021 Nov 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge Ma : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1997- |
| مواضيع طبية MeSH: | Protein Biosynthesis*/drug effects , Proteome* , Proteomics*, Mitochondria/*metabolism , Mitochondrial Proteins/*metabolism, Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology ; Electron Transport Complex I/metabolism ; Female ; HeLa Cells ; Humans ; Kinetics ; Mitochondria/drug effects ; Mitochondria/pathology ; Mitochondrial Membrane Transport Proteins/metabolism ; Protein Transport ; Uncoupling Agents/pharmacology |
| مستخلص: | Most mitochondrial proteins are translated in the cytosol and imported into mitochondria. Mutations in the mitochondrial protein import machinery cause human pathologies. However, a lack of suitable tools to measure protein uptake across the mitochondrial proteome has prevented the identification of specific proteins affected by import perturbation. Here, we introduce mePROD mt , a pulsed-SILAC based proteomics approach that includes a booster signal to increase the sensitivity for mitochondrial proteins selectively, enabling global dynamic analysis of endogenous mitochondrial protein uptake in cells. We applied mePROD mt to determine protein uptake kinetics and examined how inhibitors of mitochondrial import machineries affect protein uptake. Monitoring changes in translation and uptake upon mitochondrial membrane depolarization revealed that protein uptake was extensively modulated by the import and translation machineries via activation of the integrated stress response. Strikingly, uptake changes were not uniform, with subsets of proteins being unaffected or decreased due to changes in translation or import capacity. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Mol Cell. 2022 Jan 20;82(2):229-231. (PMID: 35063089) |
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| فهرسة مساهمة: | Keywords: SILAC; TMT; disease; integrated stress response; mitochondria; protein translocation; proteomics; proteostasis; respiratory chain complexes; translation |
| المشرفين على المادة: | 0 (Mitochondrial Membrane Transport Proteins) 0 (Mitochondrial Proteins) 0 (Proteome) 0 (Uncoupling Agents) 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone) EC 7.1.1.2 (Electron Transport Complex I) |
| تواريخ الأحداث: | Date Created: 20211130 Date Completed: 20220214 Latest Revision: 20220214 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8791276 |
| DOI: | 10.1016/j.molcel.2021.11.004 |
| PMID: | 34847359 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4164 |
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| DOI: | 10.1016/j.molcel.2021.11.004 |