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

Tommaso Pagliarusco1,2, Anais Franco-Romero1,2, Francesca Terrin3

  • 1Department of Biomedical Sciences, University of Padova, Padova, Italy.

Cell Death Discovery
|April 17, 2026
PubMed

Insights

The novel gene Mytho (Macroautophagy and YouTH Optimizer) is crucial for tissue function and DNA integrity in zebrafish. Its absence leads to increased mortality, oxidative stress, and cancer susceptibility.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • Mytho (Macroautophagy and YouTH Optimizer) is a FoxO-dependent gene regulating healthspan and lifespan via autophagy in C. elegans.
  • The role of Mytho in vertebrate tissue development and function remains uncharacterized.

Purpose of the Study:

  • To investigate the function of the Mytho gene in vertebrate development and tissue homeostasis.
  • To generate and analyze a zebrafish Mytho knockout (KO) model.

Main Methods:

  • Generation of a zebrafish Mytho KO model.
  • Assessment of mortality rates, oxidative stress resistance, larval activity, muscle structure, and tissue morphology.
  • Analysis of autophagy impairment and DNA integrity in sperm cells.

Main Results:

  • Zebrafish Mytho KO mutants exhibited increased mortality, reduced oxidative stress resistance, and impaired larval locomotor activity.
  • Adult mutants displayed altered muscle structure, autophagy impairment in key tissues (brain, muscle, testis), and tissue degeneration (pancreas, retina, muscle).
  • Mytho deficiency led to gonad alterations, reduced male reproductive capacity, increased seminoma incidence, and enhanced DNA fragmentation in sperm cells.

Conclusions:

  • Mytho plays a critical role in maintaining tissue function, DNA integrity, and reproductive health in vertebrates.
  • The study highlights Mytho's importance in preventing age-related diseases and cancer.
  • Mytho is essential for tissue homeostasis and preventing DNA damage, particularly in germ cells.

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