Communications Biology (Jan 2024)

The mitochondrial protease PARL is required for spermatogenesis

  • Sarah Schumacher,
  • Laura Klose,
  • Jessica Lambertz,
  • Dieter Lütjohann,
  • Ronald Biemann,
  • Stefanie Kuerten,
  • Lars Fester

DOI
https://doi.org/10.1038/s42003-023-05703-3
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 16

Abstract

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Abstract 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.