Temporal alterations of the nascent proteome in response to mitochondrial stress.
| Title: | Temporal alterations of the nascent proteome in response to mitochondrial stress. |
|---|---|
| Authors: | Stępkowski TM; Remedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland.; Linke V; Remedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland.; Stadnik D; Remedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland.; Zakrzewski M; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland.; Zawada AE; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland.; Serwa RA; Remedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland.; Chacinska A; Remedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland. Electronic address: a.chacinska@imol.institute. |
| Source: | Cell reports [Cell Rep] 2024 Oct 22; Vol. 43 (10), pp. 114803. Date of Electronic Publication: 2024 Oct 02. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| MeSH Terms: | Proteome*/metabolism ; Mitochondria*/metabolism ; Protein Biosynthesis* ; Stress, Physiological*; Mitochondrial Proteins/metabolism ; Ribosomal Proteins/metabolism ; Peptide Elongation Factor 1/metabolism ; Peptide Elongation Factor 1/genetics ; Humans ; HeLa Cells |
| Abstract: | Under stress, protein synthesis is attenuated to preserve energy and mitigate challenges to protein homeostasis. Here, we describe, with high temporal resolution, the dynamic landscape of changes in the abundance of proteins synthesized upon stress from transient mitochondrial inner membrane depolarization. This nascent proteome was altered when global translation was attenuated by stress and began to normalize as translation was recovering. This transition was associated with a transient desynchronization of cytosolic and mitochondrial translation and recovery of cytosolic and mitochondrial ribosomal proteins. Further, the elongation factor EEF1A1 was downregulated upon mitochondrial stress, and its silencing mimicked the stress-induced nascent proteome remodeling, including alterations in the nascent respiratory chain proteins. Unexpectedly, the stress-induced alterations in the nascent proteome were independent of physiological protein abundance and turnover. In summary, we provide insights into the physiological and pathological consequences of mitochondrial function and dysfunction.; (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Contributed Indexing: | Keywords: CP: Cell biology; CP: Metabolism; EEF1A; EEF1A1; cellular stress; elongation factor; mass spectrometry; mitochondria; nascent chain; protein synthesis; proteomics; translation |
| Substance Nomenclature: | 0 (Proteome); 0 (Mitochondrial Proteins); 0 (Ribosomal Proteins); 0 (Peptide Elongation Factor 1) |
| Entry Date(s): | Date Created: 20241003 Date Completed: 20241025 Latest Revision: 20250123 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.celrep.2024.114803 |
| PMID: | 39361503 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't