Evidence map›Paper›PMID 40339571›Full record

ArticleCurrent biology : CB2025

Biased regulation of protein synthesis and hypoxic death by a conditional raptor mutation.

Chun-Ling Sun, Cong Xu, Omar Itani, Elyse L Christensen, Harshitha Vijay, Jessica Ho, Abraham Correa-Medina, Christian B Klingler, Neal D Mathew, Stephane Flibotte and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Current biology : CB, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Raptor and Drp1 Function Synthetically to Control Hypoxic Death and the Mitochondrial Network in Caenorhabditis elegans.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Chun-Ling SunDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Cong XuDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Omar ItaniDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Elyse L ChristensenCenter for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA.
Harshitha VijayDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Jessica HoDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Abraham Correa-MedinaDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Christian B KlinglerDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Neal D MathewCenter for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA.
Stephane FlibotteLife Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Ian R HumphreysDepartment of Biochemistry, University of Washington, 1705 NE Pacific Street, Box 357350, Seattle, WA 98105, USA; Institute for Protein Design, University of Washington, 3946 W Stevens Way NE, Box 351655, Seattle, WA 98105, USA.
Diego Delgadillo RubalcabaDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Alison E RitterDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Muriel DesboisSchool of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK.
Brock GrillCenter for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA; Departments of Pediatrics and Pharmacology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
C Michael CrowderDepartment of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Box 355065, 3720 15th Avenue NE, Seattle, WA 98105, USA. Electronic address: cmc53@uw.edu.

Funding

DEFINING RAPTOR-MEDIATED MECHANISMS OF HYPOXIC INJURYR01NS128769 · NINDS · UNIVERSITY OF WASHINGTON · PI C. Michael Crowder · 2023 to 2026
$2.6M
Defining the Translational Machinery Controlling Hypoxic SensitivityR01NS109088 · NINDS · UNIVERSITY OF WASHINGTON · PI CROWDER, C. MICHAEL, VAN GILST, MARC R · 2018 to 2022
$1.9M
NIAID NIH HHS HHSN272201700059CNINDS NIH HHS R01 NS109088NINDS NIH HHS R01 NS128769
6 · The paper itself

Abstract

Mechanistic target of rapamycin (mTOR) functions in mTOR complex 1 (mTORC1) with raptor to match metazoan metabolism to available nutrients to regulate multiple cellular, physiological, and pathological processes. Hypoxic cellular injury is influenced by the mTORC1 pathway, but whether its activity promotes or prevents injury is unclear, and which mTORC1-regulated mechanisms control hypoxic injury are obscure. Here, we report the discovery of a hypoxia-resistant, temperature-sensitive raptor mutant in an unbiased forward mutagenesis screen in C. elegans. This raptor mutant is both hypoxia resistant and long lived at intermediate temperatures, while unable to develop at higher temperatures. Temperature-shift experiments show that the conditional hypoxia resistance can be induced in the raptor mutant immediately prior to the hypoxic insult. At these intermediate temperatures, the raptor mutation selectively reduces protein synthesis without affecting autophagy, and epistasis experiments implicate mTOR-targeted translation regulators as components of the hypoxia resistance mechanism. Using the conditional developmental arrest phenotype in a selection for suppressors of raptor loss of function, we isolated multiple second-site raptor missense mutants, whose mutated residue is predicted to interact with RagA, a raptor-binding protein. These suppressor mutations restore normal protein synthesis, hypoxic sensitivity, and lifespan and thereby implicate raptor-RagA interactions as critical to these biological processes.

Indexed as

Caenorhabditis elegansCaenorhabditis elegans ProteinsProtein BiosynthesisRaptorsAnimalsMechanistic Target of Rapamycin Complex 1MutationRegulatory-Associated Protein of mTORCaenorhabditis elegans ProteinsMechanistic Target of Rapamycin Complex 1Regulatory-Associated Protein of mTORanoxiaautophagyC. eleganscell deathconditional mutantmetabolismmTORmTORC1rapamycintranslation

Identifiers

PMID40339571
PMCPMC12151773

What Socratic holds

Textmetadata
LicenceTDM
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.