AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1.
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 p...
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Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009488&type=printable |
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| author | Liwei Xiao Jing Liu Zongchao Sun Yujing Yin Yan Mao Dengqiu Xu Lin Liu Zhisheng Xu Qiqi Guo Chenyun Ding Wanping Sun Likun Yang Zheng Zhou Danxia Zhou Tingting Fu Wenjing Zhou Yuangang Zhu Xiao-Wei Chen John Zhong Li Shuai Chen Xiaoduo Xie Zhenji Gan |
| author_facet | Liwei Xiao Jing Liu Zongchao Sun Yujing Yin Yan Mao Dengqiu Xu Lin Liu Zhisheng Xu Qiqi Guo Chenyun Ding Wanping Sun Likun Yang Zheng Zhou Danxia Zhou Tingting Fu Wenjing Zhou Yuangang Zhu Xiao-Wei Chen John Zhong Li Shuai Chen Xiaoduo Xie Zhenji Gan |
| author_sort | Liwei Xiao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3b1a00c5bdac44c2a91bbf246ff541a3 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-3b1a00c5bdac44c2a91bbf246ff541a32025-08-20T02:01:04ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-03-01173e100948810.1371/journal.pgen.1009488AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1.Liwei XiaoJing LiuZongchao SunYujing YinYan MaoDengqiu XuLin LiuZhisheng XuQiqi GuoChenyun DingWanping SunLikun YangZheng ZhouDanxia ZhouTingting FuWenjing ZhouYuangang ZhuXiao-Wei ChenJohn Zhong LiShuai ChenXiaoduo XieZhenji GanMitochondria 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009488&type=printable |
| spellingShingle | Liwei Xiao Jing Liu Zongchao Sun Yujing Yin Yan Mao Dengqiu Xu Lin Liu Zhisheng Xu Qiqi Guo Chenyun Ding Wanping Sun Likun Yang Zheng Zhou Danxia Zhou Tingting Fu Wenjing Zhou Yuangang Zhu Xiao-Wei Chen John Zhong Li Shuai Chen Xiaoduo Xie Zhenji Gan AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1. PLoS Genetics |
| title | AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1. |
| title_full | AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1. |
| title_fullStr | AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1. |
| title_full_unstemmed | AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1. |
| title_short | AMPK-dependent and -independent coordination of mitochondrial function and muscle fiber type by FNIP1. |
| title_sort | ampk dependent and independent coordination of mitochondrial function and muscle fiber type by fnip1 |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009488&type=printable |
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