L-2-hydroxyglutarate regulates centromere and heterochromatin conformation in the male germline.

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 chromocent

SUBMITTER: Mayorek N 

PROVIDER: S-EPMC12306753 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature