The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis Journal Article
| Authors: | Carroll, P. A.; Freie, B. W.; Cheng, P. F.; Kasinathan, S.; Gu, H.; Hedrich, T.; Dowdle, J. A.; Venkataramani, V.; Ramani, V.; Wu, X.; Raftery, D.; Shendure, J.; Ayer, D. E.; Muller, C. H.; Eisenman, R. N. |
| Article Title: | The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis |
| Abstract: | AU Male: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly germ cell (GC) production is a metabolically driven and: apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific GC transcripts and proteins. Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, obligate components of male-specific GC development, and apoptotic effectors. These in vivo and in vitro studies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors (MGCTs). © 2021 Carroll et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Journal Title: | PLoS Biology |
| Volume: | 19 |
| Issue: | 10 |
| ISSN: | 1544-9173 |
| Publisher: | Public Library of Science |
| Date Published: | 2021-10-01 |
| Start Page: | e3001085 |
| Language: | English |
| DOI: | 10.1371/journal.pbio.3001085 |
| PROVIDER: | scopus |
| PMCID: | PMC8528285 |
| PUBMED: | 34669700 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2021 -- Source: Scopus |
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