Institute of Neuroanatomy, Medical Faculty, University of Bonn, 53115, Bonn, Germany.
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127, Bonn, Germany.
Commun Biol. 2024 Jan 5;7(1):44. doi: 10.1038/s42003-023-05703-3.
Mitochondrial function plays an important role in the maintenance of male fertility. However, the mechanisms underlying mitochondrial defect-related infertility remain mostly unclear. Here we show that a deficiency of PARL (Parl), a mitochondrial protease, causes complete arrest of spermatogenesis during meiosis I. PARL deficiency led to severe downregulation of proteins of respiratory chain complex IV in testes that did not occur in other tested organs, causing a deficit in complex IV activity and ATP production. Furthermore, Parl testes showed an almost complete loss of HSD17B3, a protein of the sER responsible for the last step in testosterone synthesis. While testosterone production appeared to be restored by overexpression of HSD17B12, loss of the canonical testosterone synthesis led to an upregulation of luteinizing hormone (LH) and of LH-regulated responses. These results suggest an important impact of the downstream regulation of mitochondrial defects that manifest in a cell-type-specific manner and extend beyond mitochondria.
线粒体功能对于维持男性生育力起着重要作用。然而，线粒体缺陷相关不育的机制在很大程度上仍不清楚。在这里，我们表明线粒体蛋白酶 PARL（PARL）的缺乏会导致减数分裂 I 期间精子发生完全停滞。PARL 缺乏导致呼吸链复合物 IV 的蛋白质在睾丸中严重下调，而在其他测试器官中则不会发生这种情况，导致复合物 IV 活性和 ATP 产生不足。此外， Parl 睾丸显示出 HSD17B3 的几乎完全缺失，HSD17B3 是内质网中负责睾丸酮合成最后一步的蛋白质。虽然通过过表达 HSD17B12 似乎可以恢复睾丸酮的产生，但经典的睾丸酮合成的缺失导致黄体生成素 (LH) 的上调和 LH 调节的反应。这些结果表明，线粒体缺陷的下游调控具有重要影响，这种影响以细胞类型特异性的方式表现，并超出了线粒体的范围。
