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

ABSTRACT: Mytho (Macroautophagy and YouTH Optimizer) is a novel FoxO-dependent gene that has been recently identified to control health- and life-span in C. elegans via autophagy regulation. However, the role of this gene in tissue 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 of 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, muscle and a reduction of reproductive capabilities of males and morphological alterations in gonads of both sexes. 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.

ORGANISM(S): Danio rerio

PROVIDER: GSE317380 | GEO | 2026/04/17

REPOSITORIES: GEO

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