Meiotic activation of Mitf/TFEB declines with age in the testis.

Lysosome activity regulates germline development in multiple species. In the testis, lysosomes activate as germ cells exit mitosis and enter meiosis. Notably, reduced activity of germ-cell lysosomes, which is seen during aging, leads to fewer viable sperm. Here, we investigated the activity of Mitf/TFEB, a master regulator of lysosome biogenesis, during spermatogenesis. We discovered that Mitf activity was upregulated in meiotic-stage spermatocytes, consistent with the lysosome-activation pattern. However, Mitf activity in spermatocytes declined in older males, concurrent with reduced expression of a Mitf-targeted V-ATPase component. These findings provide insight into the regulation of upstream lysosome controls during spermatogenesis.