Adiponectin enhances the bioenergetics of cardiac myocytes via an AMPK- and succinate dehydrogenase-dependent mechanism.
Adiponectin enhances the bioenergetics of cardiac myocytes via an AMPK- and succinate dehydrogenase-dependent mechanism.
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DOI：
10.1016/j.cellsig.2020.109866
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发表时间：
2021-02
影响因子：
4.8
通讯作者：
Abdellatif, Maha
中科院分区：
文献类型：
--
作者：
Jeon, Yong Heui;He, Minzhen;Austin, Julianne;Shin, Hyewon;Pfleger, Jessica;Abdellatif, Maha
关键词：
脂联素是最丰富的循环激素之一，其通过腺苷一磷酸激活的蛋白激酶（AMPK）增强脂肪酸和葡萄糖的氧化，发挥心脏保护作用。然而，其对细胞生物能量学的影响尚未被探索。我们以前曾报道AMPK通过琥珀酸脱氢酶（SDH或复合物II）依赖性机制增强心肌细胞线粒体呼吸，这使我们预测脂联素将通过激活AMPK发挥类似的作用。我们的研究结果表明，脂联素增强基础线粒体耗氧率（OCR），ATP产生和备用呼吸能力（SRC），这些都被AMPKγ1的敲低，SDH复合物组装的抑制，通过敲低SDH组装因子1（Sdf 1），或SDH活性的抑制所消除。此外，脂联素缓解缺氧诱导的OCR和ATP生产的减少，在SdAL 1依赖的方式，而SdAL 1的过表达证实了其足以介导这些影响。重要的是，各种条件下的全酶SDH水平与OCR相关。我们还表明，脂联素，AMPK，Sdalphin 1，以及SDH复合物组装的影响都需要sirtuin 3（Sirt 3）。总之，在心肌细胞中，脂联素通过促进SDH复合物以AMPK-、Sdf 1-和Sirt 3-依赖的方式组装而增强线粒体生物能量学。
Adiponectin is one of the most abundant circulating hormones, which through adenosine monophosphate-activated protein kinase (AMPK), enhances fatty acid and glucose oxidation, and exerts a cardioprotective effect. However, its effects on cellular bioenergetics have not been explored. We have previously reported that AMPK enhances mitochondrial respiration through a succinate dehydrogenase (SDH or complex II)-dependent mechanism in cardiac myocytes, leading us to predict that Adiponectin would exert a similar effect via activating AMPK. Our results show that Adiponectin enhances basal mitochondrial oxygen consumption rate (OCR), ATP production, and spare respiratory capacity (SRC), which were all abolished by the knockdown of AMPKγ1, inhibition of SDH complex assembly, via the knockdown of the SDH assembly factor 1 (Sdhaf1), or inhibition of SDH activity. Additionally, Adiponectin alleviated hypoxia-induced reductions in OCR and ATP production, in a Sdhaf1-dependent manner, whereas overexpression of Sdhaf1 confirmed its sufficiency for mediating these effects. Importantly, the levels of holoenzyme SDH under the various conditions correlated with OCR. We also show that the effects of Adiponectin, AMPK, Sdhaf1, as well as, SDH complex assembly all required sirtuin 3 (Sirt3). In conclusion, Adiponectin potentiates mitochondrial bioenergetics via promoting SDH complex assembly in an AMPK-, Sdhaf1-, and Sirt3-dependent fashion in cardiac myocytes.
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影响因子：
16
作者：
Hirschey MD;Shimazu T;Jing E;Grueter CA;Collins AM;Aouizerat B;Stančáková A;Goetzman E;Lam MM;Schwer B;Stevens RD;Muehlbauer MJ;Kakar S;Bass NM;Kuusisto J;Laakso M;Alt FW;Newgard CB;Farese RV Jr;Kahn CR;Verdin E
通讯作者：
Verdin E
影响因子：
7.4
作者：
Flynn, James M.;Choi, Sung W.;Day, Nicholas U.;Gerencser, Akos A.;Hubbard, Alan;Melov, Simon
通讯作者：
Melov, Simon
影响因子：
3.7
作者：
Hill BG;Benavides GA;Lancaster JR Jr;Ballinger S;Dell'Italia L;Jianhua Z;Darley-Usmar VM
通讯作者：
Darley-Usmar VM
影响因子：
30.8
作者：
BOURGERON, T;RUSTIN, P;ROTIG, A
通讯作者：
ROTIG, A
DOI：
10.1152/ajpendo.00086.2010
发表时间：
2010-11-01
影响因子：
5.1
作者：
Fang, Xiangping;Palanivel, Rengasamy;Sweeney, Gary
通讯作者：
Sweeney, Gary