Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing.
Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing.
复制标题
巢蛋白依赖性睾丸激素受体接触定义干细胞间质细胞分化，以减轻男性生殖衰老。
DOI：
10.1038/s41467-022-31755-w
复制
发表时间：
2022-07-11
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
男性生殖系统衰老与睾丸激素产生不足密切相关，睾丸激素产生不足是由于功能性间质细胞（从干间质细胞（SLC）分化而来）的丧失。然而，SLC分化和衰老之间的关系仍然未知。此外，生殖系统中SLC分化期间的活性脂质代谢需要在多个细胞器之间运输和加工底物，例如，线粒体和内质网（ER），强调细胞器间接触的重要性。在这里，我们表明，SLC分化潜力下降，细胞内稳态紊乱，在SLC衰老。从机制上讲，中间丝巢蛋白的损失通过在SLC衰老期间分离细胞-ER接触（MERC）而导致较低的分化能力。此外，褪黑激素的药物干预恢复巢蛋白依赖的MERC，逆转SLC分化能力和延缓男性生殖系统衰老。这些发现不仅从细胞因子依赖的MERC调节机制解释了SLC衰老，而且还提出了一种有希望的针对SLC分化的治疗方法，用于治疗年龄相关的生殖系统疾病。导致男性生殖老化的调节机制尚不清楚。在这里，作者表明，巢蛋白依赖性线粒体-内质网接触（MERCs）调节干Leydig细胞（SLC）衰老，并提供了对SLC靶向治疗的见解。
Male reproductive system ageing is closely associated with deficiency in testosterone production due to loss of functional Leydig cells, which are differentiated from stem Leydig cells (SLCs). However, the relationship between SLC differentiation and ageing remains unknown. In addition, active lipid metabolism during SLC differentiation in the reproductive system requires transportation and processing of substrates among multiple organelles, e.g., mitochondria and endoplasmic reticulum (ER), highlighting the importance of interorganelle contact. Here, we show that SLC differentiation potential declines with disordered intracellular homeostasis during SLC senescence. Mechanistically, loss of the intermediate filament Nestin results in lower differentiation capacity by separating mitochondria-ER contacts (MERCs) during SLC senescence. Furthermore, pharmacological intervention by melatonin restores Nestin-dependent MERCs, reverses SLC differentiation capacity and alleviates male reproductive system ageing. These findings not only explain SLC senescence from a cytoskeleton-dependent MERCs regulation mechanism, but also suggest a promising therapy targeting SLC differentiation for age-related reproductive system diseases. The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.
登录
查看更多内容
DOI：
10.1083/jcb.200911024
发表时间：
2010-08-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Friedman JR;Webster BM;Mastronarde DN;Verhey KJ;Voeltz GK
通讯作者：
Voeltz GK
PTPRO 通过 ERBB2 的去磷酸化和内体内化来抑制 ERBB2 驱动的乳腺肿瘤发生
影响因子：
8
作者：
Dong H;Ma L;Gan J;Lin W;Chen C;Yao Z;Du L;Zheng L;Ke C;Huang X;Song H;Kumar R;Yeung SC;Zhang H
通讯作者：
Zhang H
DOI：
10.1001/jama.2016.21043
发表时间：
2017-02-21
期刊：
JAMA
影响因子：
--
作者：
Budoff MJ;Ellenberg SS;Lewis CE;Mohler ER 3rd;Wenger NK;Bhasin S;Barrett-Connor E;Swerdloff RS;Stephens-Shields A;Cauley JA;Crandall JP;Cunningham GR;Ensrud KE;Gill TM;Matsumoto AM;Molitch ME;Nakanishi R;Nezarat N;Matsumoto S;Hou X;Basaria S;Diem SJ;Wang C;Cifelli D;Snyder PJ
通讯作者：
Snyder PJ
影响因子：
8.8
作者：
Atkins KM;Thomas LL;Barroso-González J;Thomas L;Auclair S;Yin J;Kang H;Chung JH;Dikeakos JD;Thomas G
通讯作者：
Thomas G
巢蛋白阳性干间质细胞作为治疗睾丸间质细胞功能障碍的潜在来源的表征。
影响因子：
44.1
作者：
通讯作者：
--