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在睾丸中,Mitf/TFEB的减数分裂激活随年龄增长而下降。

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

作者信息

Butsch Tyler J, Johnson Alyssa E, Bohnert K Adam

机构信息

Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, United States.

出版信息

MicroPubl Biol. 2025 Feb 7;2025. doi: 10.17912/micropub.biology.001509. eCollection 2025.

DOI:10.17912/micropub.biology.001509
PMID:39989905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11845987/
Abstract

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.

摘要

溶酶体活性调节多种物种的生殖细胞发育。在睾丸中,随着生殖细胞退出有丝分裂并进入减数分裂,溶酶体被激活。值得注意的是,生殖细胞溶酶体活性降低(在衰老过程中可见)会导致有活力的精子数量减少。在这里,我们研究了溶酶体生物发生的主要调节因子Mitf/TFEB在精子发生过程中的活性。我们发现,Mitf活性在减数分裂期的精母细胞中上调,这与溶酶体激活模式一致。然而,老年雄性动物精母细胞中的Mitf活性下降,同时Mitf靶向的V-ATP酶成分的表达也降低。这些发现为精子发生过程中上游溶酶体控制的调节提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2439/11845987/99dec5d60b9b/25789430-2025-micropub.biology.001509.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2439/11845987/99dec5d60b9b/25789430-2025-micropub.biology.001509.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2439/11845987/99dec5d60b9b/25789430-2025-micropub.biology.001509.jpg

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本文引用的文献

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Biol Futur. 2022 Jun;73(2):187-204. doi: 10.1007/s42977-022-00122-7. Epub 2022 Jun 7.
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A meiotic switch in lysosome activity supports spermatocyte development in young flies but collapses with age.溶酶体活性的减数分裂开关在年轻果蝇中支持精母细胞发育,但随着年龄增长而瓦解。
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A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage.
一项遗传筛选鉴定了卵母细胞成熟过程中的新步骤,这些步骤增强了永生生殖系中的蛋白质稳态。
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Programmed cell death 4 modulates lysosomal function by inhibiting TFEB translation.程序性细胞死亡蛋白 4 通过抑制 TFEB 翻译来调节溶酶体功能。
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Lysosomes as dynamic regulators of cell and organismal homeostasis.溶酶体作为细胞和整体内稳态的动态调节剂。
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Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal.鞘脂类调节激活蛋白质稳态程序以调控人类造血干细胞自我更新。
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Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3.溶酶体信号通过失活 Tfe3 来启动胚胎干细胞分化。
Cell Stem Cell. 2019 Feb 7;24(2):257-270.e8. doi: 10.1016/j.stem.2018.11.021. Epub 2018 Dec 27.
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