AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1.
AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1.
复制标题
FNIP1 对线粒体功能和肌纤维类型的 AMPK 依赖性和非依赖性协调
DOI：
10.1371/journal.pgen.1009488
复制
发表时间：
2021-03
期刊：
影响因子：
4.5
通讯作者：
Gan Z
中科院分区：
文献类型：
--
作者：
Xiao L;Liu J;Sun Z;Yin Y;Mao Y;Xu D;Liu L;Xu Z;Guo Q;Ding C;Sun W;Yang L;Zhou Z;Zhou D;Fu T;Zhou W;Zhu Y;Chen XW;Li JZ;Chen S;Xie X;Gan Z
线粒体是维持骨骼肌代谢平衡的必要条件，在适应性反应过程中，以无数的生理或病理生理压力。线粒体功能和收缩纤维类型协调调节以确保肌肉功能的机制仍然知之甚少。有证据表明，Fnip 1与骨骼肌纤维类型、功能和疾病有关。在这项研究中，Fnip 1特异性表达于Fnip 1转基因（Fnip 1 Tg）小鼠的骨骼肌中。将Fnip 1 Tg小鼠与Fnip 1敲除（Fnip 1 KO）小鼠杂交，以产生仅在骨骼肌中表达Fnip 1而不在其他组织中表达Fnip 1的Fnip 1 TgKO小鼠。我们的研究结果表明，除了在I型纤维程序中的已知作用外，FNIP 1通过AMPK信号传导对肌肉线粒体氧化程序施加控制。事实上，FNIP 1的基础水平足以抑制骨骼肌细胞中AMPK的活性，但不能抑制mTORC 1的活性。在小鼠中的功能获得和功能丧失策略，以及对原代肌细胞的评估，表明骨骼肌线粒体程序通过FNIP 1对AMPK的抑制作用而被抑制。令人惊讶的是，FNIP 1对I型纤维的作用不依赖于AMPK及其下游的PGC-1α。这些研究为理解FNIP 1作为决定肌肉适应性的线粒体功能和肌纤维类型的协调调节的关键因素的内在作用提供了重要框架。
Mitochondria are essential for maintaining skeletal muscle metabolic homeostasis during adaptive response to a myriad of physiologic or pathophysiological stresses. The mechanisms by which mitochondrial function and contractile fiber type are concordantly regulated to ensure muscle function remain poorly understood. Evidence is emerging that the Folliculin interacting protein 1 (Fnip1) is involved in skeletal muscle fiber type specification, function, and disease. In this study, Fnip1 was specifically expressed in skeletal muscle in Fnip1-transgenic (Fnip1Tg) mice. Fnip1Tg mice were crossed with Fnip1-knockout (Fnip1KO) mice to generate Fnip1TgKO mice expressing Fnip1 only in skeletal muscle but not in other tissues. Our results indicate that, in addition to the known role in type I fiber program, FNIP1 exerts control upon muscle mitochondrial oxidative program through AMPK signaling. Indeed, basal levels of FNIP1 are sufficient to inhibit AMPK but not mTORC1 activity in skeletal muscle cells. Gain-of-function and loss-of-function strategies in mice, together with assessment of primary muscle cells, demonstrated that skeletal muscle mitochondrial program is suppressed via the inhibitory actions of FNIP1 on AMPK. Surprisingly, the FNIP1 actions on type I fiber program is independent of AMPK and its downstream PGC-1α. These studies provide a vital framework for understanding the intrinsic role of FNIP1 as a crucial factor in the concerted regulation of mitochondrial function and muscle fiber type that determine muscle fitness.
登录
查看更多内容
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1083/jcb.201712177
发表时间：
2018-08-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Meng J;Ferguson SM
通讯作者：
Ferguson SM
组蛋白甲基转移酶 MLL4 通过 MEF2 相互作用控制肌纤维特性和肌肉性能
影响因子：
15.9
作者：
Liu, Lin;Ding, Chenyun;Gan, Zhenji
通讯作者：
Gan, Zhenji
IRE1 α-XBP1s 轴将 COPII 囊泡运输与营养可用性耦合
DOI：
10.1073/pnas.1814480116
发表时间：
2019-06-11
影响因子：
11.1
作者：
Liu, Lin;Cai, Jie;Gan, Zhenji
通讯作者：
Gan, Zhenji
影响因子：
16
作者：
Bruning, JC;Michael, MD;Kahn, CR
通讯作者：
Kahn, CR