Autophagy-related proteins are functionally active in human spermatozoa and may be involved in the regulation of cell survival and motility.
Autophagy-related proteins are functionally active in human spermatozoa and may be involved in the regulation of cell survival and motility.
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DOI：
10.1038/srep33647
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发表时间：
2016-09-16
影响因子：
4.6
通讯作者：
Tapia JA
中科院分区：
文献类型：
--
作者：
Aparicio IM;Espino J;Bejarano I;Gallardo-Soler A;Campo ML;Salido GM;Pariente JA;Peña FJ;Tapia JA
巨自噬（以下简称自噬）是一种进化上高度保守的细胞过程，通过降解大多数长寿蛋白质和整个细胞器参与细胞内稳态的维持。自噬参与一些生殖事件；然而，目前还没有关于自噬在精子生理调节中的作用的报道。因此，本研究的目的是调查人类精子中是否存在自噬相关蛋白并具有功能活性。人类精子中存在与自噬/线粒体自噬过程相关的蛋白质（LC3、Atg5、Atg16、Beclin 1、p62、m-TOR、AMPKα 1/2 和 PINK1）。 LC3 与 p62 共定位于精子的中部。自噬激活导致运动显着增加，PINK1、TOM20 表达和 caspase 3/7 激活减少。相反，自噬抑制导致运动性、活力、ATP 和细胞内钙浓度降低，而 PINK1、TOM20 表达、AMPK 磷酸化和 caspase 3/7 激活显着增加。总之，我们的结果表明自噬相关蛋白和上游调节因子在人类精子中存在并发挥作用。自噬激活/抑制后线粒体蛋白表达的改变可能表明一种称为线粒体自噬的特殊形式的自噬可能正在调节精子功能，如运动性和活力，并可能与细胞凋亡相配合。
Macroautophagy (hereafter autophagy) is an evolutionarily highly conserved cellular process that participates in the maintenance of intracellular homeostasis through the degradation of most long-lived proteins and entire organelles. Autophagy participates in some reproductive events; however, there are not reports regarding the role of autophagy in the regulation of sperm physiology. Hence, the aim of this study was to investigate whether autophagy-related proteins are present and functionally active in human spermatozoa. Proteins related to autophagy/mitophagy process (LC3, Atg5, Atg16, Beclin 1, p62, m-TOR, AMPKα 1/2, and PINK1) were present in human spermatozoa. LC3 colocalized with p62 in the middle piece of the spermatozoa. Autophagy activation induced a significant increase in motility and a decrease in PINK1, TOM20 expression and caspase 3/7 activation. In contrast, autophagy inhibition resulted in decreased motility, viability, ATP and intracellular calcium concentration whereas PINK1, TOM20 expression, AMPK phosphorylation and caspase 3/7 activation were significantly increased. In conclusion our results show that autophagy related proteins and upstream regulators are present and functional in human spermatozoa. Modification of mitochondrial proteins expression after autophagy activation/inhibition may be indicating that a specialized form of autophagy named mitophagy may be regulating sperm function such as motility and viability and may be cooperating with apoptosis.
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