In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2021-8-5), p. e1009688-
Abstract:
Autophagy degrades unnecessary proteins or damaged organelles to maintain cellular function. Therefore, autophagy has a preventive role against various diseases including hepatic disorders, neurodegenerative diseases, and cancer. Although autophagy in germ cells or Sertoli cells is known to be required for spermatogenesis and male fertility, it remains poorly understood how autophagy participates in spermatogenesis. We found that systemic knockout mice of Rubicon , a negative regulator of autophagy, exhibited a substantial reduction in testicular weight, spermatogenesis, and male fertility, associated with upregulation of autophagy. Rubicon -null mice also had lower levels of mRNAs of Sertoli cell–related genes in testis. Importantly, Rubicon knockout in Sertoli cells, but not in germ cells, caused a defect in spermatogenesis and germline stem cell maintenance in mice, indicating a critical role of Rubicon in Sertoli cells. In mechanistic terms, genetic loss of Rubicon promoted autophagic degradation of GATA4, a transcription factor that is essential for Sertoli cell function. Furthermore, androgen antagonists caused a significant decrease in the levels of Rubicon and GATA4 in testis, accompanied by elevated autophagy. Collectively, we propose that Rubicon promotes Sertoli cell function by preventing autophagic degradation of GATA4, and that this mechanism could be regulated by androgens.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009688
DOI:
10.1371/journal.pgen.1009688.g001
DOI:
10.1371/journal.pgen.1009688.g002
DOI:
10.1371/journal.pgen.1009688.g003
DOI:
10.1371/journal.pgen.1009688.g004
DOI:
10.1371/journal.pgen.1009688.g005
DOI:
10.1371/journal.pgen.1009688.g006
DOI:
10.1371/journal.pgen.1009688.g007
DOI:
10.1371/journal.pgen.1009688.s001
DOI:
10.1371/journal.pgen.1009688.s002
DOI:
10.1371/journal.pgen.1009688.s003
DOI:
10.1371/journal.pgen.1009688.s004
DOI:
10.1371/journal.pgen.1009688.s005
DOI:
10.1371/journal.pgen.1009688.s006
DOI:
10.1371/journal.pgen.1009688.s007
DOI:
10.1371/journal.pgen.1009688.s008
DOI:
10.1371/journal.pgen.1009688.s009
DOI:
10.1371/journal.pgen.1009688.s010
DOI:
10.1371/journal.pgen.1009688.r001
DOI:
10.1371/journal.pgen.1009688.r002
DOI:
10.1371/journal.pgen.1009688.r003
DOI:
10.1371/journal.pgen.1009688.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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