Ubiquitin Ligase Nrdp1 Controls Autophagy-Associated Acrosome Biogenesis and Mitochondrial Arrangement during Spermiogenesis

Autophagy is critical to acrosome biogenesis and mitochondrial quality control, but the underlying mechanisms remain unclear. The ubiquitin ligase Nrdp1/RNF41 promotes ubiquitination of the mitophagy-associated Parkin and interacts with the pro-autophagic protein SIP/CacyBP. Here, we report that global deletion of Nrdp1 leads to formation of the round-headed sperm and male infertility by disrupting autophagy. Quantitative proteome analyses demonstrated that the expression of many proteins associated with mitochondria, lysosomes, and acrosomes was dysregulated in either spermatids or sperm of the Nrdp1-deficient mice. Deletion of Nrdp1 increased the levels of Parkin but decreased the levels of SIP, the mitochondrial fission protein Drp1 and the mitochondrial protein Tim23 in sperm, accompanied by the inhibition of autophagy, the impairment of acrosome biogenesis and the disruption of mitochondrial arrangement in sperm. Thus, our results uncover an essential role of Nrdp1 in spermiogenesis and male fertility by promoting autophagy, providing important clues to cope with the related male reproductive diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Cells - 12(2023), 18 vom: 05. Sept.

Sprache:

Englisch

Beteiligte Personen:

Luo, Zi-Yu [VerfasserIn]
Jiang, Tian-Xia [VerfasserIn]
Zhang, Tao [VerfasserIn]
Xu, Ping [VerfasserIn]
Qiu, Xiao-Bo [VerfasserIn]

Links:

Volltext

Themen:

Acrosome
Autophagy
EC 2.3.2.27
Journal Article
Mitochondrium
Mitophagy
Nrdp1
Parkin
Research Support, Non-U.S. Gov't
Rnf41 protein, mouse
SIP/CacyBP
Spermiogenesis
Ubiquitin ligase
Ubiquitin-Protein Ligases

Anmerkungen:

Date Completed 05.10.2023

Date Revised 05.10.2023

published: Electronic

Citation Status MEDLINE

doi:

10.3390/cells12182211

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM362556997