MOTS-c 通过直接结合和激活 CK2 来调节骨骼肌功能。

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2024-10-19 eCollection Date: 2024-11-15 DOI:10.1016/j.isci.2024.111212

Hiroshi Kumagai, Su-Jeong Kim, Brendan Miller, Hirofumi Zempo, Kumpei Tanisawa, Toshiharu Natsume, Shin Hyung Lee, Junxiang Wan, Naphada Leelaprachakul, Michi Emma Kumagai, Ricardo Ramirez, Hemal H Mehta, Kevin Cao, Tae Jung Oh, James A Wohlschlegel, Jihui Sha, Yuichiro Nishida, Noriyuki Fuku, Shohei Dobashi, Eri Miyamoto-Mikami, Mizuki Takaragawa, Mizuho Fuku, Toshinori Yoshihara, Hisashi Naito, Ryoko Kawakami, Suguru Torii, Taishi Midorikawa, Koichiro Oka, Megumi Hara, Chiharu Iwasaka, Yosuke Yamada, Yasuki Higaki, Keitaro Tanaka, Kelvin Yen, Pinchas Cohen

{"title":"MOTS-c 通过直接结合和激活 CK2 来调节骨骼肌功能。","authors":"Hiroshi Kumagai, Su-Jeong Kim, Brendan Miller, Hirofumi Zempo, Kumpei Tanisawa, Toshiharu Natsume, Shin Hyung Lee, Junxiang Wan, Naphada Leelaprachakul, Michi Emma Kumagai, Ricardo Ramirez, Hemal H Mehta, Kevin Cao, Tae Jung Oh, James A Wohlschlegel, Jihui Sha, Yuichiro Nishida, Noriyuki Fuku, Shohei Dobashi, Eri Miyamoto-Mikami, Mizuki Takaragawa, Mizuho Fuku, Toshinori Yoshihara, Hisashi Naito, Ryoko Kawakami, Suguru Torii, Taishi Midorikawa, Koichiro Oka, Megumi Hara, Chiharu Iwasaka, Yosuke Yamada, Yasuki Higaki, Keitaro Tanaka, Kelvin Yen, Pinchas Cohen","doi":"10.1016/j.isci.2024.111212","DOIUrl":null,"url":null,"abstract":"MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems. MOTS-c administration to mice prevented skeletal muscle atrophy and enhanced muscle glucose uptake, which were blunted by suppressing CK2 activity. Interestingly, the effects of MOTS-c are tissue-specific. Systemically administered MOTS-c binds to CK2 in fat and muscle, yet stimulates CK2 activity in muscle while suppressing it in fat by differentially modifying CK2-interacting proteins. Notably, a naturally occurring MOTS-c variant, K14Q MOTS-c, has reduced binding to CK2 and does not activate it or elicit its effects. Male K14Q MOTS-c carriers exhibited a higher risk of sarcopenia and type 2 diabetes (T2D) in an age- and physical-activity-dependent manner, whereas females had an age-specific reduced risk of T2D. Altogether, these findings provide evidence that CK2 is required for MOTS-c effects.","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 11","pages":"111212"},"PeriodicalIF":4.6000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570452/pdf/","citationCount":"0","resultStr":"{\"title\":\"MOTS-c modulates skeletal muscle function by directly binding and activating CK2.\",\"authors\":\"Hiroshi Kumagai, Su-Jeong Kim, Brendan Miller, Hirofumi Zempo, Kumpei Tanisawa, Toshiharu Natsume, Shin Hyung Lee, Junxiang Wan, Naphada Leelaprachakul, Michi Emma Kumagai, Ricardo Ramirez, Hemal H Mehta, Kevin Cao, Tae Jung Oh, James A Wohlschlegel, Jihui Sha, Yuichiro Nishida, Noriyuki Fuku, Shohei Dobashi, Eri Miyamoto-Mikami, Mizuki Takaragawa, Mizuho Fuku, Toshinori Yoshihara, Hisashi Naito, Ryoko Kawakami, Suguru Torii, Taishi Midorikawa, Koichiro Oka, Megumi Hara, Chiharu Iwasaka, Yosuke Yamada, Yasuki Higaki, Keitaro Tanaka, Kelvin Yen, Pinchas Cohen\",\"doi\":\"10.1016/j.isci.2024.111212\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems. MOTS-c administration to mice prevented skeletal muscle atrophy and enhanced muscle glucose uptake, which were blunted by suppressing CK2 activity. Interestingly, the effects of MOTS-c are tissue-specific. Systemically administered MOTS-c binds to CK2 in fat and muscle, yet stimulates CK2 activity in muscle while suppressing it in fat by differentially modifying CK2-interacting proteins. Notably, a naturally occurring MOTS-c variant, K14Q MOTS-c, has reduced binding to CK2 and does not activate it or elicit its effects. Male K14Q MOTS-c carriers exhibited a higher risk of sarcopenia and type 2 diabetes (T2D) in an age- and physical-activity-dependent manner, whereas females had an age-specific reduced risk of T2D. Altogether, these findings provide evidence that CK2 is required for MOTS-c effects.\",\"PeriodicalId\":342,\"journal\":{\"name\":\"iScience\",\"volume\":\"27 11\",\"pages\":\"111212\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570452/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"iScience\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.isci.2024.111212\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/15 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.isci.2024.111212","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/15 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

MOTS-c 是一种能改善新陈代谢的线粒体微蛋白。在这里，我们证明了 CK2 是 MOTS-c 的直接功能靶标。MOTS-c 可直接与 CK2 结合，并在无细胞系统中激活 CK2。给小鼠注射 MOTS-c 可防止骨骼肌萎缩并增强肌肉葡萄糖摄取，而抑制 CK2 的活性则会减弱这种作用。有趣的是，MOTS-c 的作用具有组织特异性。全身给药的 MOTS-c 可与脂肪和肌肉中的 CK2 结合，但在肌肉中会刺激 CK2 的活性，而在脂肪中则会通过对 CK2 相互作用蛋白的不同修饰而抑制 CK2 的活性。值得注意的是，一种天然存在的 MOTS-c 变异体 K14Q MOTS-c 与 CK2 的结合减少，不会激活 CK2 或引起其效应。男性 K14Q MOTS-c 基因携带者患肌肉疏松症和 2 型糖尿病（T2D）的风险较高，且与年龄和体力活动有关，而女性患 T2D 的风险则随着年龄的增长而降低。总之，这些发现提供了 CK2 是 MOTS-c 作用所必需的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

MOTS-c modulates skeletal muscle function by directly binding and activating CK2.

MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems. MOTS-c administration to mice prevented skeletal muscle atrophy and enhanced muscle glucose uptake, which were blunted by suppressing CK2 activity. Interestingly, the effects of MOTS-c are tissue-specific. Systemically administered MOTS-c binds to CK2 in fat and muscle, yet stimulates CK2 activity in muscle while suppressing it in fat by differentially modifying CK2-interacting proteins. Notably, a naturally occurring MOTS-c variant, K14Q MOTS-c, has reduced binding to CK2 and does not activate it or elicit its effects. Male K14Q MOTS-c carriers exhibited a higher risk of sarcopenia and type 2 diabetes (T2D) in an age- and physical-activity-dependent manner, whereas females had an age-specific reduced risk of T2D. Altogether, these findings provide evidence that CK2 is required for MOTS-c effects.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.