摘要：SummaryGamete development ultimately influences animal fertility. Identifying mechanisms that direct gametogenesis, and how they deteriorate with age, may inform ways to combat infertility. Recently, we found that lysosomes acidify during oocyte maturation inCaenorhabditis elegans, suggesting that a meiotic switch in lysosome activity promotes female germ-cell health. UsingDrosophila melanogaster, we report that lysosomes likewise acidify in male germ cells during meiosis. Inhibiting lysosomes in young-male testes causes E-cadherin accumulation and loss of germ-cell partitioning membranes. Notably, analogous changes occur naturally during aging; in older testes, a reduction in lysosome acidity precedes E-cadherin accumulation and membrane dissolution, suggesting one potential cause of age-related spermatocyte abnormalities. Consistent with lysosomes governing the production of mature sperm, germ cells with homozygous-null mutations in lysosome-acidifying machinery fail to survive through meiosis. Thus, lysosome activation is entrained to meiotic progression in developing sperm, as in oocytes, and lysosomal dysfunction may instigate male reproductive aging.Graphical abstractDisplay OmittedHighlights•Lysosomes acidify at the mitotic-meiotic transition in the testis•Acidic lysosomes support germ-cell membrane stability•Lysosome acidity naturally declines in the aging male germline•Lysosome acidification is required for mature sperm productionBiological sciences; Molecular biology; Cell biology; Developmental biology
