안용진 (서울대학교) | 한빛사논문 > 한빛사

한빛사논문

조회468

서울대학교

Exp. Mol. Med., 02 October 2023 | https://doi.org/10.1038/s12276-023-01095-w Lactate as a major epigenetic carbon source for histone acetylation via nuclear LDH metabolism

Yong Jin An ¹, Sihyang Jo ¹, Jin-Mo Kim ¹, Han Sun Kim ¹, Hyun Young Kim ², Sang-Min Jeon ^2,3, Dawool Han ⁴, Jong In Yook ⁴, Keon Wook Kang ² and Sunghyouk Park ^1,*

¹Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
²College of Pharmacy, Seoul National University, Seoul 08826, Korea.
³College of Pharmacy and Institute of Pharmaceutical Science and Technology, Ajou University, Gyeonggi-do 16499, Korea.
⁴Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, Korea.

^*Corresponding author: correspondence to Sunghyouk Park

Abstract

Histone acetylation involves the transfer of two-carbon units to the nucleus that are embedded in low-concentration metabolites. We found that lactate, a high-concentration metabolic byproduct, can be a major carbon source for histone acetylation through oxidation-dependent metabolism. Both in cells and in purified nuclei, ¹³C₃-lactate carbons are incorporated into histone H4 (maximum incorporation: ~60%). In the purified nucleus, this process depends on nucleus-localized lactate dehydrogenase (LDHA), knockout (KO) of which abrogates incorporation. Heterologous expression of nucleus-localized LDHA reverses the KO effect. Lactate itself increases histone acetylation, whereas inhibition of LDHA reduces acetylation. In vitro and in vivo settings exhibit different lactate incorporation patterns, suggesting an influence on the microenvironment. Higher nuclear LDHA localization is observed in pancreatic cancer than in normal tissues, showing disease relevance. Overall, lactate and nuclear LDHA can be major structural and regulatory players in the metabolism–epigenetics axis controlled by the cell’s own status or the environmental status.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-04)
연구진국내 연구진
분야 생명과학 > 생화학

댓글 작성 로그인

CV 열람하기

연락처 보기