A meiotic switch in lysosome activity supports spermatocyte development in young flies but collapses with age.
A meiotic switch in lysosome activity supports spermatocyte development in young flies but collapses with age.
复制标题
溶酶体活动中的减数分裂开关支持幼蝇精母细胞的发育，但随着年龄的增长而崩溃。
DOI：
10.1016/j.isci.2022.104382
复制
发表时间：
2022-06-17
期刊：
影响因子：
5.8
通讯作者：
Bohnert, K. Adam
中科院分区：
文献类型：
--
作者：
Butsch, Tyler J.;Dubuisson, Olga;Johnson, Alyssa E.;Bohnert, K. Adam
配子的发育最终影响动物的生育能力。确定直接配子发生的机制，以及它们如何随着年龄的增长而恶化，可能会为对抗不孕症提供方法。最近，我们发现秀丽隐杆线虫在卵母细胞成熟过程中溶酶体酸化，这表明溶酶体活性的减数分裂开关促进了雌性生殖细胞的健康。利用黑腹果蝇，我们报道了在减数分裂过程中，溶酶体同样在雄性生殖细胞中酸化。抑制溶酶体在年轻男性睾丸导致e -钙粘蛋白积累和生殖细胞分划膜的损失。值得注意的是，类似的变化在衰老过程中自然发生；在老年睾丸中，溶酶体酸度的降低先于e-钙粘蛋白积累和膜溶解，提示与年龄相关的精细胞异常的一个潜在原因。与溶酶体控制成熟精子的产生一致，溶酶体酸化机制中纯合零突变的生殖细胞不能通过减数分裂存活。因此，在发育中的精子中，溶酶体的激活与减数分裂过程有关，就像在卵母细胞中一样，溶酶体功能障碍可能会引发男性生殖衰老。溶酶体在睾丸有丝分裂-减数分裂转变时酸化酸性溶酶体支持生殖细胞膜的稳定性在男性生殖系衰老时溶酶体酸度自然下降溶酶体酸化是成熟精子生产所必需的生物科学；分子生物学;细胞生物学;发育生物学
Gamete 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 in Caenorhabditis elegans, suggesting that a meiotic switch in lysosome activity promotes female germ-cell health. Using Drosophila 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. 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 production Biological sciences; Molecular biology; Cell biology; Developmental biology
登录
查看更多内容
影响因子：
3.7
作者：
Castro-Gomes T;Corrotte M;Tam C;Andrews NW
通讯作者：
Andrews NW
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.7
作者：
Fabrizio, JJ;Boyle, M;DiNardo, S
通讯作者：
DiNardo, S
影响因子：
3.3
作者：
Baxi, Kunal;Ghavidel, Ata;de Carvalho, Carlos E.
通讯作者：
de Carvalho, Carlos E.
影响因子：
64.8
作者：
Bohnert KA;Kenyon C
通讯作者：
Kenyon C