Evidence map›Paper›PMID 39107687›Full record

ArticleBMC genomics2024

Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.

Yevgeniy Raynes, John C Santiago, Faye A Lemieux, Leah Darwin, David M Rand

Abstract read
In one paragraph

Article in BMC genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
  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

5 authors.

Yevgeniy RaynesDepartment of Ecology, Evolution, and Organismal Biology, Brown University, Providence, RI, 02912, USA. yevgeniy_raynes@brown.edu.
John C SantiagoDepartment of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, RI, 02912, USA.
Faye A LemieuxDepartment of Ecology, Evolution, and Organismal Biology, Brown University, Providence, RI, 02912, USA.
Leah DarwinDepartment of Ecology, Evolution, and Organismal Biology, Brown University, Providence, RI, 02912, USA.
David M RandDepartment of Ecology, Evolution, and Organismal Biology, Brown University, Providence, RI, 02912, USA. david_rand@brown.edu.

Funding

The role of Sirtuins in neurodegenerative diseaseP20GM109035 · NIGMS · BROWN UNIVERSITY · PI WU, ZHIJIN JEAN · 2016 to 2025
$22.6M
Nuclear-Mitochondrial Fitness Interactions in DrosophilaR01GM067862 · NIGMS · BROWN UNIVERSITY · PI RAND, DAVID M · 2004 to 2020
$5.1M
Mitonuclear genetics of complex traits in DrosophilaR35GM139607 · NIGMS · BROWN UNIVERSITY · PI RAND, DAVID M · 2021 to 2025
$1.9M
Mitochondrial genes and TOR signaling in DrosophilaF31GM117851 · NIGMS · BROWN UNIVERSITY · PI SANTIAGO, JOHN C. · 2016 to 2018
$128k
NIGMS NIH HHS F31 GM117851NIGMS NIH HHS P20 GM109035NIGMS NIH HHS R01 GM067862NIGMS NIH HHS R35 GM139607
6 · The paper itself

Abstract

backgroundMany common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies.

resultsWe assayed gene expression with and without rapamycin exposure across three distinct body parts (head, thorax, abdomen) of D. melanogaster flies, bearing either their native melanogaster mitochondrial genome or the mitochondrial genome from a related species, D. simulans. The fully factorial RNA-seq study design revealed a large number of genes that responded to the rapamycin treatment in a sex-dependent and tissue-dependent manner, and relatively few genes with the transcriptional response to rapamycin affected by the mitochondrial background. Reanalysis of an earlier study confirmed that mitochondria can have a temporal influence on rapamycin response.

conclusionsWe found significant and wide-ranging effects of sex and body part, alongside a subtle, potentially time-dependent, influence of mitochondria on the transcriptional response to rapamycin. Our findings suggest a number of pathways that could be crucial for predicting potential side effects of mTOR inhibition in a particular sex or tissue. Further studies of the temporal response to rapamycin are necessary to elucidate the effects of the mitochondrial background on mTOR and its inhibition.

Indexed as

MitochondriaSirolimusAnimalsDrosophilaDrosophila melanogasterFemaleGene Expression ProfilingMaleOrgan SpecificitySex FactorsTOR Serine-Threonine KinasesTranscription, GeneticSirolimusTOR Serine-Threonine KinasesInteractionsMitonuclear genotypemTORPersonalized medicineRapamycinSexTissue

Identifiers

PMID39107687
PMCPMC11304892

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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.