Evidence map›Paper›PMID 41315397›Full record

ArticleNature communications2025

TOR and heat shock response pathways regulate peroxisome biogenesis during proteotoxic stress.

Nandini Shukla, Maxwell L Neal, Jean-Claude Farré, Fred D Mast, Rajasri Sarkar, Linh Truong, Theresa Simon, Leslie R Miller, John D Aitchison, Suresh Subramani

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. More than the 'master regulator of cytosolic proteostasis': new roles for HSF1 in promoting tissue health.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
    Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Nandini ShuklaDepartment of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. nandini.shukla@unt.edu.ORCID http://orcid.org/0000-0003-2750-229X
Maxwell L NealCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2390-6572
Jean-Claude FarréDepartment of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Fred D MastCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2177-6647
Rajasri SarkarDepartment of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Linh TruongDepartment of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Theresa SimonDepartment of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Leslie R MillerCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
John D AitchisonCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9153-6497
Suresh SubramaniDepartment of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. ssubramani@ucsd.edu.ORCID http://orcid.org/0000-0003-0180-1742

Funding

TARGETING OF PROTEINS INTO PEROXISOMESR01DK041737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AITCHISON, JOHN D., SUBRAMANI, SURESH · 1990 to 2025
$8.4M
Targeting of proteins into peroxisomesR37DK041737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANI, SURESH · 2004 to 2013
$5.3M
Targeting of Proteins into PeroxisomesR56DK041737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANI, SURESH · 2014 to 2014
$149k
NIDDK NIH HHS R01 DK041737NIDDK NIH HHS R37 DK041737NIDDK NIH HHS R56 DK041737U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK41737
6 · The paper itself

Abstract

Peroxisomes are versatile organelles mediating energy homeostasis and redox balance. While peroxisome dysfunction is linked to numerous diseases, the mechanisms regulating peroxisome dynamics during cellular stress remain elusive. Using yeast, we show that proteotoxic stress, including loss of endoplasmic reticulum (ER) or cytosolic chaperone function, impaired ER protein translocation, disrupted N-linked glycosylation, or reductive stress, triggers peroxisome proliferation. This occurs through increased de novo biogenesis from the ER, as well as growth and division, rather than impaired pexophagy. Peroxisome biogenesis is essential for cellular recovery from proteotoxic stress. Through comprehensive testing of major signaling pathways, we determine this response to be mediated by activation of the heat shock response and inhibition of Target of Rapamycin (TOR) signaling. Notably, the effects of proteotoxic stress and TOR inhibition on peroxisomes are also observed in human fibroblasts. Our findings reveal a critical and conserved role of peroxisomes in cellular response to proteotoxic stress.

Indexed as

Heat-Shock ResponseOrganelle BiogenesisPeroxisomesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTOR Serine-Threonine KinasesEndoplasmic ReticulumEndoplasmic Reticulum StressFibroblastsHumansProteotoxic StressSignal TransductionSaccharomyces cerevisiae ProteinsTOR Serine-Threonine Kinases

Identifiers

PMID41315397
PMCPMC12663454

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.