| Autor: |
Ke Cao, Weiqiang Lv, Xueqiang Wang, Shanshan Dong, Xuyun Liu, Tielin Yang, Jie Xu, Mengqi Zeng, Xuan Zou, Daina Zhao, Qingqing Ma, Mu Lin, Jiangang Long, Weijin Zang, Feng Gao, Zhihui Feng, Jiankang Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Advanced Science, Vol 8, Iss 11, Pp n/a-n/a (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202004507 |
| Popis: |
Abstract Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5’‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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