ArticleNature2015
Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 261 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
261 citing papers in PubMed, 469 citations in OpenAlex.
- Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in men.Nature communications · 2025Trial
- The role and mechanism of UPRmt in adipocytes.Adipocyte · 2026Review
- Small molecules rescue pathogenic POLGA aggregation and restore its functions in a mouse model of PEO.EMBO molecular medicine · 2026Article
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Chromatin stability safeguards mitochondrial homeostasis and restrains TORC1 signaling.PLoS genetics · 2026Article
- Ubiquitination-mediated degradation of NLRX1 drives metabolic vulnerability and accelerates intervertebral disc degeneration.Cell death and differentiation · 2026Article
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Adaptation of OXPHOS biogenesis to cellular requirements.Protein science : a publication of the Protein Society · 2026Review
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Mitochondrial Localization and Abundance of Leishmania Cytochrome c Oxidase Subunit IV Is Maintained Following Loss of Mitochondrial Membrane Potential Associated With Mammalian Temperature.Molecular microbiology · 2026Article
- Redox signals and oxidative stress in the control of mitochondrial protein import.Protein science : a publication of the Protein Society · 2026Review
- Mass spectrometry proteomics for studying mitostasis.Protein science : a publication of the Protein Society · 2026Review
- Co-translational protein targeting to mitochondria in the context of co-translational protein maturation.Protein science : a publication of the Protein Society · 2026Review
- Integrated analysis of the redoxome and zinc proteome links ribosomal protein oxidation to zinc homeostasis.Redox biology · 2026Article
- Mitochondrial protein import stress causes lysosomal damage and progressive tissue atrophy.EMBO reports · 2026Article
- The role of the nucleus in the control of mitochondrial precursor proteins in yeast.Protein science : a publication of the Protein Society · 2026Review
- Perturbation of mitochondrial CaStress biology · 2026Article
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- Proteolytic control of mitochondrial protein translocases.Protein science : a publication of the Protein Society · 2026Review
- mtHsp70 chaperone converts mitochondrial proteostasis stress into impaired protein import.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
201 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most of the mitochondrial proteome originates from nuclear genes and is transported into the mitochondria after synthesis in the cytosol. Complex machineries which maintain the specificity of protein import and sorting include the TIM23 translocase responsible for the transfer of precursor proteins into the matrix, and the mitochondrial intermembrane space import and assembly (MIA) machinery required for the biogenesis of intermembrane space proteins. Dysfunction of mitochondrial protein sorting pathways results in diminishing specific substrate proteins, followed by systemic pathology of the organelle and organismal death. The cellular responses caused by accumulation of mitochondrial precursor proteins in the cytosol are mainly unknown. Here we present a comprehensive picture of the changes in the cellular transcriptome and proteome in response to a mitochondrial import defect and precursor over-accumulation stress. Pathways were identified that protect the cell against mitochondrial biogenesis defects by inhibiting protein synthesis and by activation of the proteasome, a major machine for cellular protein clearance. Proteasomal activity is modulated in proportion to the quantity of mislocalized mitochondrial precursor proteins in the cytosol. We propose that this type of unfolded protein response activated by mistargeting of proteins (UPRam) is beneficial for the cells. UPRam provides a means for buffering the consequences of physiological slowdown in mitochondrial protein import and for counteracting pathologies that are caused or contributed by mitochondrial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.