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Mytho/Phaf1 is required to prevent DNA damage and tissue degeneration in Danio rerio.

Overview

Authors: Tommaso Pagliarusco1,2, Anais Franco-Romero1,2, Francesca Terrin3, Filippo Citton1, Ludovica Carducci1, Nicola Facchinello4,5, Camilla Maria Fontana3, Marta Giacomazzo6, Ranieri Verin7, Maria Berica Rasotto3, Lisa Locatello8, Luisa Dalla Valle3, Marco Sandri1,2,9
  1. Department of Biomedical Sciences, University of Padova, Padova, Italy
  2. Veneto Institute of Molecular Medicine, Padova, Italy
  3. Department of Biology, University of Padova, Padova, Italy
  4. Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
  5. Neuroscience Institute, Italian Research Council (CNR), Padova, Italy
  6. Department of Comparative Biomedicine and Food Science (BCA), University of Padova, Legnaro, PD Italy
  7. Department of Veterinary Sciences, University of Pisa, Pisa, Italy
  8. Stazione Zoologica Anton Dohrn, Department of Biology and Evolution of Marine Organisms, Fano Marine Center, Fano, Italy
  9. Department of Medicine, McGill University, Montreal, QC Canada
Journal: Cell death discovery, volume 12, issue 1, article 252
Dates: received 3 November 2025; accepted 26 March 2026; published online 17 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41420-026-03106-x · PMID 41997945 · PMCID PMC13212566 · OpenAlex W7154699556
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: zebrafish (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials, Connectivity
Keywords: Macroautophagy, Infertility, Ageing
Topic: FOXO transcription factor regulation (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Fondazione Cassa di Risparmio di Padova e Rovigo
Citations: not cited yet (Europe PMC); 50 references in the paper

Abstract

mytho (Macroautophagy and YouTH Optimizer) is a novel FoxO-dependent gene that has been recently identified to control health- and life-span in Caenorhabditis elegans via autophagy regulation. However, the role of this gene in tissues development and function in vertebrates has not yet been established. To address these issues, we generated a zebrafish mytho KO model and observed that mutants exhibited a higher mortality rate than wild-type (WT) siblings during the first month of life and a lower resistance to oxidative stress. mytho silencing resulted in a decrease in larval locomotor activity and muscle birefringence and caused alteration of adult muscle structure. Autophagy impairment was confirmed in tissues with the highest mytho expression such as brain, muscle and testis. Finally, mutants showed tissue degeneration in pancreas, retina and muscle, morphological alterations in gonads of both sexes and a reduction of reproductive capabilities of males. Importantly, males presented a higher incidence of seminomas, a testicular cancer. The increased susceptibility to cancer is associated with an enhanced DNA fragmentation in sperm cells. In conclusion, this study highlights the key role of Mytho in maintaining proper tissue function and DNA integrity.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

The datasets generated and analyzed during the current study are available in NCBI’s Gene Expression Omnibus (Edgar et al., 2002) and are accessible through GEO Series accession number GSE317380 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317380) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317380).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 3 keywords, 1 funder, 46 references.

Cite

This paper

Pagliarusco, T., Franco-Romero, A., Terrin, F., Citton, F., Carducci, L., Facchinello, N., Fontana, C. M., Giacomazzo, M., Verin, R., Rasotto, M. B., Locatello, L., Dalla Valle, L., & Sandri, M. (2026). Mytho/Phaf1 is required to prevent DNA damage and tissue degeneration in Danio rerio. Cell death discovery, 12(1), 252. https://doi.org/10.1038/s41420-026-03106-x

BibTeX

@article{pagliarusco2026mytho,
author = {Pagliarusco, Tommaso and Franco-Romero, Anais and Terrin, Francesca and Citton, Filippo and Carducci, Ludovica and Facchinello, Nicola and Fontana, Camilla Maria and Giacomazzo, Marta and Verin, Ranieri and Rasotto, Maria Berica and Locatello, Lisa and Dalla Valle, Luisa and Sandri, Marco},
title = {{Mytho/Phaf1 is required to prevent DNA damage and tissue degeneration in Danio rerio}},
journal = {Cell death discovery},
year = {2026},
month = apr,
volume = {12},
number = {1},
pages = {252},
publisher = {Nature Publishing Group},
issn = {2058-7716},
doi = {10.1038/s41420-026-03106-x},
url = {https://doi.org/10.1038/s41420-026-03106-x},
pmid = {41997945},
pmcid = {PMC13212566}
}

RIS

TY - JOUR
AU - Pagliarusco, Tommaso
AU - Franco-Romero, Anais
AU - Terrin, Francesca
AU - Citton, Filippo
AU - Carducci, Ludovica
AU - Facchinello, Nicola
AU - Fontana, Camilla Maria
AU - Giacomazzo, Marta
AU - Verin, Ranieri
AU - Rasotto, Maria Berica
AU - Locatello, Lisa
AU - Dalla Valle, Luisa
AU - Sandri, Marco
TI - Mytho/Phaf1 is required to prevent DNA damage and tissue degeneration in Danio rerio
T2 - Cell death discovery
J2 - Cell Death Discov
PY - 2026
DA - 2026/04/17
VL - 12
IS - 1
SP - 252
SN - 2058-7716
PB - Nature Publishing Group
DO - 10.1038/s41420-026-03106-x
UR - https://doi.org/10.1038/s41420-026-03106-x
LA - en
ER -

CSL-JSON

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