ArticlePLoS genetics2025
L-2-hydroxyglutarate regulates centromere and heterochromatin conformation in the male germline.
Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Comparative study on the functions of LDHA and LDHC in triple-negative breast cancer.Discover oncology · 2026Article
- Transcriptome profiling of histone writers/erasers enzymes across spermatogenesis, mature sperm and pre-cleavage embryo: Implications in paternal epigenome transitions and inheritance mechanisms.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
19 authors.
Funding
Abstract
Germ cell differentiation in the male testis involves extensive phenotypic, transcriptional, and epigenetic modifications, which are essential for producing functional spermatozoa. Among all organs, the testis exhibits the highest baseline physiological levels of L-2-hydroxyglutarate (L-2HG), yet its role in male germ cell development remains unknown. Here, we reveal that L-2HG is synthesized during the pachytene and diplotene stages of meiosis by the testis-specific enzyme lactate dehydrogenase C (LDHC). Surprisingly, LDHC translocates into the nucleus, localizing along the synaptonemal complex and at centromeres. L-2HG, produced by LDHC, regulates centromere condensation and heterochromatin organization via multiple mechanisms, including chromocenter clustering, centromere and chromocenter condensation, and modulation of satellite RNA expression. These effects are rapid, specific to L-2HG, and independent of histone methylation changes. Acute depletion of L-2HG in vivo results in centromere dysfunction and activation of the spindle assembly checkpoint (SAC), suggesting the possible role of this metabolite in ensuring proper chromosome segregation.
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Registered trials
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