Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (674 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Regulation of the concentration, folding, interactions, and cellular localization of each of the proteins that comprise the proteome.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Proteostases; Protein Homeostasis; Homeostases, Protein; Homeostasis, Protein; Protein Homeostases.
Where it fits in the MeSH classification
- Broader topics
- Biochemical Phenomena; Metabolism
- See also
- Protein Folding; Proteostasis Deficiencies
Related concepts
- Proteome
Research landscape
PubMed indexes 2,138 records tagged with the MeSH heading “Proteostasis” (counts retrieved 2026-10-29). 1,597 of them (74.7%) were published from 2020 onward, and the busiest period so far is 2020 onward with 1,597 records.
Reviews account for 756 records (35.4%) and meta-analyses for 5. Randomized controlled trials number 3 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 0 |
| 2010-2019 | 570 |
| 2020 onward | 1,597 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 756 | 35.4% |
| Meta-analyses | 5 | 0.2% |
| Randomized controlled trials | 3 | 0.1% |
Method: PubMed query "Proteostasis"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease | 2025 | Research article Design not recorded in structured metadata | 83 | cc by PMID 40140603 · DOI · PMC11991917 |
| Regulation of mitochondrial proteostasis by the proton gradient | 2022 | Research article Design not recorded in structured metadata | 81 | cc by PMID 35912435 · DOI · PMC9379554 |
| Global and tissue-specific aging effects on murine proteomes | 2023 | Research article Design not recorded in structured metadata | 69 | cc by PMID 37405913 · DOI · PMC10588767 |
| GCN2 in proteostasis: structural logic, signalling networks and disease | 2026 | Review article Design not recorded in structured metadata | 8 | cc by PMID 41782119 · DOI · PMC13580269 |
Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Ageing is the most prominent risk factor for Alzheimer's disease (AD).
- Closing excerpt
- Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of ageing and AD.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (164 words)
Ageing is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and amyloid β, resembling those in APP mouse brains and the brains of patients with AD. Quantitative tNeuron proteomics identify ageing- and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Providing support for the centrality of lysosomal deficits in AD, compounds ameliorating lysosomal function reduce amyloid β deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of ageing and AD.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40140603 · DOI · PMC11991917
Regulation of mitochondrial proteostasis by the proton gradient [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Mitochondria adapt to different energetic demands reshaping their proteome.
- Closing excerpt
- TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (159 words)
Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multiproteomic approach to demonstrate the regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+ /H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35912435 · DOI · PMC9379554
Global and tissue-specific aging effects on murine proteomes [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Maintenance of protein homeostasis degrades with age, contributing to aging-related decline and disease.
- Closing excerpt
- These data provide a foundation for understanding how proteins contribute to systemic aging across tissues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Maintenance of protein homeostasis degrades with age, contributing to aging-related decline and disease. Previous studies have primarily surveyed transcriptional aging changes. To define the effects of age directly at the protein level, we perform discovery-based proteomics in 10 tissues from 20 C57BL/6J mice, representing both sexes at adult and late midlife ages (8 and 18 months). Consistent with previous studies, age-related changes in protein abundance often have no corresponding transcriptional change. Aging results in increases in immune proteins across all tissues, consistent with a global pattern of immune infiltration with age. Our protein-centric data reveal tissue-specific aging changes with functional consequences, including altered endoplasmic reticulum and protein trafficking in the spleen. We further observe changes in the stoichiometry of protein complexes with important roles in protein homeostasis, including the CCT/TriC complex and large ribosomal subunit. These data provide a foundation for understanding how proteins contribute to systemic aging across tissues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37405913 · DOI · PMC10588767
GCN2 in proteostasis: structural logic, signalling networks and disease [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Proteostasis is the finely tuned balance of protein synthesis, folding and degradation essential for cellular health.
- Closing excerpt
- In this review, we explore how GCN2 links nutrient sensing to translational control and metabolic adaptation, and how its central role in proteostasis may inform new strategies for treating diseases driven by protein misfolding and stress pathway imbalance.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (201 words)
Proteostasis is the finely tuned balance of protein synthesis, folding and degradation essential for cellular health. When this equilibrium is disrupted, misfolded proteins accumulate, triggering adaptive stress responses such as the unfolded protein response and the integrated stress response (ISR). Central to the ISR is the kinase GCN2, a sensor of amino acid deprivation and ribosomal stress. Upon activation, GCN2 phosphorylates eIF2α, dampening global translation while selectively enhancing the synthesis of the stress-responsive transcription factors ATF4 and CHOP. ATF4 orchestrates a broad transcriptional programme that supports amino acid metabolism, redox homeostasis, autophagy and proteasomal degradation, which are key processes for restoring proteostasis. Beyond its canonical role, GCN2 interfaces with other regulatory networks modulating mTORC1 to promote autophagic clearance of damaged proteins and organelles, facilitating stress granule formation, and integrating signals from oxidative and endoplasmic reticulum stress to rebalance the proteome. Dysregulated GCN2 activity has been implicated in diverse pathologies including neurodegeneration, cancer and pulmonary vascular disease, positioning it as a promising therapeutic target. In this review, we explore how GCN2 links nutrient sensing to translational control and metabolic adaptation, and how its central role in proteostasis may inform new strategies for treating diseases driven by protein misfolding and stress pathway imbalance.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41782119 · DOI · PMC13580269
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article The proteostasis network and its decline in ageing [5]
- Research article The integrated stress response: From mechanism to disease [6]
- Research article Pathways of cellular proteostasis in aging and disease [7]
- Research article DNA damage-how and why we age? [8]
- Research article Proteostasis, oxidative stress and aging [9]
- Research article Functional Modules of the Proteostasis Network [10]
References
- Chou CC, Vest R, Prado MA, Wilson-Grady J, Paulo JA, Shibuya Y, et al.. Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease. . 2025. PMID 40140603 · DOI · PMC11991917
- Patron M, Tarasenko D, Nolte H, Kroczek L, Ghosh M, Ohba Y, et al.. Regulation of mitochondrial proteostasis by the proton gradient. . 2022. PMID 35912435 · DOI · PMC9379554
- Keele GR, Zhang JG, Szpyt J, Korstanje R, Gygi SP, Churchill GA, et al.. Global and tissue-specific aging effects on murine proteomes. . 2023. PMID 37405913 · DOI · PMC10588767
- Zhu J, Marciniak SJ. GCN2 in proteostasis: structural logic, signalling networks and disease. . 2026. PMID 41782119 · DOI · PMC13580269
- Hipp MS, Kasturi P, Hartl FU. The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol. 2019. PMID 30733602 · DOI
- Costa-Mattioli M, Walter P. The integrated stress response: From mechanism to disease. Science. 2020. PMID 32327570 · DOI · PMC8997189
- Klaips CL, Jayaraj GG, Hartl FU. Pathways of cellular proteostasis in aging and disease. J Cell Biol. 2018. PMID 29127110 · DOI · PMC5748993
- Yousefzadeh M, Henpita C, Vyas R, Soto-Palma C, Robbins P, Niedernhofer L. DNA damage-how and why we age?. Elife. 2021. PMID 33512317 · DOI · PMC7846274
- Korovila I, Hugo M, Castro JP, Weber D, Höhn A, Grune T, et al.. Proteostasis, oxidative stress and aging. Redox Biol. 2017. PMID 28763764 · DOI · PMC5536880
- Jayaraj GG, Hipp MS, Hartl FU. Functional Modules of the Proteostasis Network. Cold Spring Harb Perspect Biol. 2020. PMID 30833457 · DOI · PMC6942124
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.