Evidence map›Paper›PMID 38405984›Full record

ArticlebioRxiv : the preprint server for biology2024

Translational response to mitochondrial stresses is orchestrated by tRNA modifications.

Sherif Rashad, Shadi Al-Mesitef, Abdulrahman Mousa, Yuan Zhou, Daisuke Ando, Guangxin Sun, Tomoko Fukuuchi, Yuko Iwasaki, Jingdong Xiang, Shane R Byrne and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. 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 at 6 institutions in 3 countries.

Sherif RashadDepartment of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.ORCID 0000-0002-4511-6360
Shadi Al-MesitefDepartment of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Abdulrahman MousaDepartment of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Yuan ZhouDepartment of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Daisuke AndoDepartment of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Guangxin SunDepartment of Biological Engineering, Massachusetts Institute of Technology, MA, USA.
Tomoko FukuuchiLaboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan.
Yuko IwasakiLaboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan.
Jingdong XiangDepartment of Biological Engineering, Massachusetts Institute of Technology, MA, USA.
Shane R ByrneDepartment of Biological Engineering, Massachusetts Institute of Technology, MA, USA.
Jingjing SunDepartment of Biological Engineering, Massachusetts Institute of Technology, MA, USA.
Masamitsu MaekawaDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Daisuke SaigusaLaboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan.
Thomas J BegleyDepartment of Biological Sciences, University at Albany, Albany, NY, USA.
Peter C DedonDepartment of Biological Engineering, Massachusetts Institute of Technology, MA, USA.ORCID 0000-0003-0011-3067
Kuniyasu NiizumaDepartment of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Tohoku University · JPTeikyo University · JPMassachusetts Institute of Technology · USSingapore-MIT Alliance for Research and Technology · SGBiomedical Research Models (United States) · USUniversity at Albany, State University of New York · US

Funding

TRAINING GRANTS IN ENVIROMENTAL TOXICOLOGYT32ES007020 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2024
$13.1M
NIEHS NIH HHS T32 ES007020
6 · The paper itself

Abstract

Mitochondrial stress and dysfunction play important roles in many pathologies. However, how cells respond to mitochondrial stress is not fully understood. Here, we examined the translational response to electron transport chain (ETC) inhibition and arsenite induced mitochondrial stresses. Our analysis revealed that during mitochondrial stress, tRNA modifications (namely f5C, hm5C, queuosine and its derivatives, and mcm5U) dynamically change to fine tune codon decoding, usage, and optimality. These changes in codon optimality drive the translation of many pathways and gene sets, such as the ATF4 pathway and selenoproteins, involved in the cellular response to mitochondrial stress. We further examined several of these modifications using targeted approaches. ALKBH1 knockout (KO) abrogated f5C and hm5C levels and led to mitochondrial dysfunction, reduced proliferation, and impacted mRNA translation rates. Our analysis revealed that tRNA queuosine (tRNA-Q) is a master regulator of the mitochondrial stress response. KO of QTRT1 or QTRT2, the enzymes responsible for tRNA-Q synthesis, led to mitochondrial dysfunction, translational dysregulation, and metabolic alterations in mitochondria-related pathways, without altering cellular proliferation. In addition, our analysis revealed that tRNA-Q loss led to a domino effect on various tRNA modifications. Some of these changes could be explained by metabolic profiling. Our analysis also revealed that utilizing serum deprivation or alteration with Queuine supplementation to study tRNA-Q or stress response can introduce various confounding factors by altering many other tRNA modifications. In summary, our data show that tRNA modifications are master regulators of the mitochondrial stress response by driving changes in codon decoding.

Indexed as

Codon usageMitochondrial stressmRNA translationOxidative stressQueuineQueuosineRNA modificationstRNAtRNA modifications

Identifiers

PMID38405984
PMCPMC10888749
OpenAlexW4391838245

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.