The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
A mitochondrial specific stress response in mammalian cells
Open accessAbstract
Cells respond to a wide variety of stresses through the transcriptional activation of genes that harbour stress elements within their promoters. While many of these elements are shared by genes encoding proteins representative of all subcellular compartments, cells can also respond to stresses that are specific to individual organelles, such as the endoplasmic reticulum un folded protein response. Here we report on the discovery and characterization of a mitochondrial stress response in mammalian cells. We find that the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional upregulation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ and ClpP, but not those encoding stress proteins of the endoplasmic reticulum. Analysis of the chaperonin 60/10 bidirectional promoter identified a CHOP element as the mitochondrial stress response element. Dominant-negative mutant forms of CHOP and overexpression of CHOP revealed that this transcription factor, in association with C/EBPbeta, regulates expression of mitochondrial stress genes in response to the accumulation of unfolded proteins.
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“Under stress conditions, when the degradation pathways are insufficient to repair the consequences of the alteration in mitochondrial translation [52] or the accumulation of oxidatively damaged or misfolded proteins, a retrograde signal is activated which coordinates nuclear gene expression. This mitochondria-to- nucleus response is named mitochondrial unfolding protein response (UPRmt) [53].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [53]
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“Under stress conditions, UPRmt occurs in an attempt to maintain mitochondrial proteostasis by upregulating the expression of mitochondrial chaperones and m-AAA proteases (e.g., chaperonin 10, chaperonin 60, and CLPP) (69).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [69]
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“a known protein degraded by LONP1 and an established model for studying mitochondrial proteostasis imbalance38–40”
From Disuse-associated loss of the protease Lonp1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength (2022) · cites this paper as [38]
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Metadata
- Authors
- Zhao, Q., Wang, J., Levichkin, I. V., Stasinopoulos, S., Ryan, M. T., & Hoogenraad, N. J.
- Affiliations
- La Trobe University (AU)
- Corresponding author
- Hoogenraad, Nicholas J.
- ORCID
- Zhao, Quan
- Venue
- The EMBO Journal
- Published
- 2002-09-02
- Volume
- 21
- Issue
- 17
- Pages
- 4411-4419
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC126185
- OpenAlex
- W2108738634
- Cited by
- 1,026
- References
- 55
- Citations by year
- 2026: 58 · 2025: 64 · 2024: 71 · 2023: 59 · 2022: 71 · 2021: 88 · 2020: 77 · 2019: 60 · 2018: 60 · 2017: 46 · 2016: 50 · 2015: 42 · 2014: 45 · 2013: 38 · 2012: 29
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial stress response, unfolded protein accumulation, mitochondrial matrix, CHOP, C/EBPβ, transcriptional regulation, chaperonin 60, GroES, ClpP, unfolded protein response, mammalian cells
- MeSH terms
- Adenosine Triphosphatases, Animals, Cell Nucleus, Chlorocebus aethiops, Gene Expression Regulation, Genes, Dominant, Heat-Shock Proteins, Mitochondria, Ornithine Carbamoyltransferase, Promoter Regions, Genetic, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Serine Endopeptidases, Stress, Physiological, Transcription Factors, Transcription, Genetic, Transfection, Signal Transduction, Sequence Deletion, Protein Folding, Chaperonin 60, Chaperonin 10, COS Cells, Protein Transport, CCAAT-Enhancer-Binding Proteins, Endopeptidase Clp, HSP40 Heat-Shock Proteins, Transcription Factor CHOP
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