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Cited by 69Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyHeat shock proteins research

Mechanisms Linking Mitochondrial Dysfunction and Proteostasis Failure

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Lu, Bingwei, Guo, Su·2020·Trends in Cell Biology
DOI 10.1016/j.tcb.2020.01.008PMC PMC7093050
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Abstract

Maintaining cellular protein homeostasis (proteostasis) is an essential task for all eukaryotes. Proteostasis failure worsens with aging and is considered a cause of and a therapeutic target for age-related diseases including neurodegenerative disorders. The cellular networks regulating proteostasis and the pathogenic events driving proteostasis failure in disease remain poorly understood. Model organism studies in yeast and Drosophila reveal an intriguing link between mitochondrial function and proteostasis. In this review we examine recent findings on mitochondrial outer membrane (MOM)-associated mRNA translation, how this process is sensitive to mitochondrial dysfunction and constantly surveyed by ribosome-associated quality control (RQC), and how defects in this process generate aberrant proteins with unusual C-terminal extensions (CTEs) that promote aggregation and drive proteostasis failure. We also discuss the implications for human diseases.

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  • Spaceflight induces proteostasis failure.

    “Specifically, we found ribosome assembly, mitochondrial, and cytosolic translation pathways altered, implying proteostasis failure induced by spaceflight (Lu and Guo, 2020).”

    From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Lu and Guo, 2020

    The Abstract and ‘An Intimate Connection between Mitochondrial Function and Cytosolic Proteostasis’ section link mitochondrial dysfunction and disrupted translation or ribosome quality control to proteostasis failure (page numbers unavailable). This supports the citing authors’ interpretation of the altered pathways, but the source does not address spaceflight or establish that spaceflight induces proteostasis failure. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Mitochondrial dysfunction inhibits cytosolic protein synthesis and defective protein quality control.

    “Mitochondrial dysfunction inhibits cytosolic protein synthesis and defective protein quality control (Lu and Guo, 2020; Topf et al., 2019).”

    From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Lu and Guo, 2020

    The section “Mitochondrial Outer Membrane-Associated Translation is Stalled by Mitochondrial Stress” (page unavailable) reports that persistent mitochondrial damage stalls translation of a specific mRNA at the mitochondrial outer membrane. The paper also links mitochondrial stress to altered protein quality control, but it does not establish that mitochondrial dysfunction broadly inhibits cytosolic protein synthesis or necessarily makes protein quality control defective. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Alterations in ribosome assembly, mitochondrial, and cytosol translation pathways in cell models, internal organs, and muscles suggest proteostasis failure.

    “Alterations in ribosome assembly, mitochondrial, and cytosol translation pathway in the cell models, internal organs, and muscles (Figs. 2 and 3) suggest the presence of proteostasis failure (Lu and Guo, 2020).”

    From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Lu and Guo, 2020

    The Abstract and “An Intimate Connection between Mitochondrial Function and Cytosolic Proteostasis” (pages not provided) link disrupted mitochondrial function and translation quality control to proteostasis failure. They do not establish that the particular pathway alterations observed in the citing paper’s cell models, internal organs, and muscles indicate proteostasis failure, and they do not specifically address ribosome assembly alterations. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Lu, B., & Guo, S.
Affiliations
  • Stanford Medicine (US)
  • University of California, San Francisco (US)
Corresponding author
Lu, Bingwei
ORCID
Venue
Trends in Cell Biology
Publisher
Elsevier BV
Published
2020-04
Volume
30
Issue
4
Pages
317-328
ISSN
0962-8924 (ISSN-L)
DOI
10.1016/j.tcb.2020.01.008
PMC
PMC7093050
OpenAlex
W3005825727
Cited by
69
References
11
Citations by year
2026: 16 · 2025: 16 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 1
FWCI
0.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Trends in Cell Biology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • US Department of Defense
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
mitochondrial dysfunction, proteostasis, mitochondrial outer membrane, mRNA translation, ribosome-associated quality control, C-terminal extension, protein aggregation, aging, age-related neurodegenerative diseases, yeast, Drosophila
MeSH terms
Proteostasis, Animals, Cytosol, Humans, Mitochondria, Models, Biological, Ribosomes, Mitochondrial Membranes

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