PHAF1/MYTHO is a novel autophagy regulator that controls muscle integrity.

IF 14.6 1区 生物学 Q1 CELL BIOLOGY
Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-12 DOI:10.1080/15548627.2023.2224206
Anais Franco-Romero, Jean Philippe Leduc-Gaudet, Sabah Na Hussain, Gilles Gouspillou, Marco Sandri
{"title":"PHAF1/MYTHO is a novel autophagy regulator that controls muscle integrity.","authors":"Anais Franco-Romero, Jean Philippe Leduc-Gaudet, Sabah Na Hussain, Gilles Gouspillou, Marco Sandri","doi":"10.1080/15548627.2023.2224206","DOIUrl":null,"url":null,"abstract":"<p><p>Skeletal muscles play key roles in movement, posture, thermogenesis, and whole-body metabolism. Autophagy plays essential roles in the regulation of muscle mass, function and integrity. However, the molecular machinery that regulates autophagy is still incompletely understood. In our recent study, we identified and characterized a novel Forkhead Box O (FoxO)-dependent gene, PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), as a novel autophagy regulator that controls muscle integrity. MYTHO/PHAF1 is upregulated in multiple conditions leading to muscle atrophy, and downregulation of its expression spares muscle atrophy triggered by fasting, denervation, cachexia and sepsis. Overexpression of PHAF1/MYTHO is sufficient to induce muscle atrophy. Prolonged downregulation of PHAF1/MYTHO causes a severe myopathic phenotype, which is characterized by impaired autophagy, muscle weakness, myofiber degeneration, mammalian target of rapamycin complex 1 (mTORC1) hyperactivation and extensive ultrastructural defects, such as accumulation of proteinaceous and membranous structures and tubular aggregates. This myopathic phenotype is attenuated upon administration of the mTORC1 inhibitor rapamycin. These findings position PHAF1/MYTHO as a novel regulator of skeletal muscle autophagy and tissue integrity.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":14.6000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062385/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autophagy","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15548627.2023.2224206","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Skeletal muscles play key roles in movement, posture, thermogenesis, and whole-body metabolism. Autophagy plays essential roles in the regulation of muscle mass, function and integrity. However, the molecular machinery that regulates autophagy is still incompletely understood. In our recent study, we identified and characterized a novel Forkhead Box O (FoxO)-dependent gene, PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), as a novel autophagy regulator that controls muscle integrity. MYTHO/PHAF1 is upregulated in multiple conditions leading to muscle atrophy, and downregulation of its expression spares muscle atrophy triggered by fasting, denervation, cachexia and sepsis. Overexpression of PHAF1/MYTHO is sufficient to induce muscle atrophy. Prolonged downregulation of PHAF1/MYTHO causes a severe myopathic phenotype, which is characterized by impaired autophagy, muscle weakness, myofiber degeneration, mammalian target of rapamycin complex 1 (mTORC1) hyperactivation and extensive ultrastructural defects, such as accumulation of proteinaceous and membranous structures and tubular aggregates. This myopathic phenotype is attenuated upon administration of the mTORC1 inhibitor rapamycin. These findings position PHAF1/MYTHO as a novel regulator of skeletal muscle autophagy and tissue integrity.

PHAF1/MYTHO 是一种新型自噬调节因子,可控制肌肉的完整性。
骨骼肌在运动、姿势、产热和全身新陈代谢中发挥着关键作用。自噬在调节肌肉质量、功能和完整性方面发挥着至关重要的作用。然而,人们对调控自噬的分子机制仍然知之甚少。在最近的研究中,我们发现并鉴定了一种新型叉头框 O(FoxO)依赖基因 PHAF1/MYTHO(吞噬细胞组装因子 1/宏观自噬和青年优化因子),它是一种新型自噬调节因子,可控制肌肉的完整性。MYTHO/PHAF1在多种导致肌肉萎缩的情况下上调,而下调其表达则可避免因禁食、去神经、恶病质和败血症引发的肌肉萎缩。PHAF1/MYTHO 的过表达足以诱发肌肉萎缩。PHAF1/MYTHO 的长期下调会导致严重的肌病表型,其特征是自噬功能受损、肌肉无力、肌纤维变性、雷帕霉素靶点复合体 1(mTORC1)过度激活和广泛的超微结构缺陷,如蛋白质和膜结构的堆积以及管状聚集。这种肌病表型在服用 mTORC1 抑制剂雷帕霉素后有所减轻。这些发现使 PHAF1/MYTHO 成为骨骼肌自噬和组织完整性的新型调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Autophagy
Autophagy 生物-细胞生物学
CiteScore
21.30
自引率
2.30%
发文量
277
审稿时长
1 months
期刊介绍: Autophagy is a peer-reviewed journal that publishes research on autophagic processes, including the lysosome/vacuole dependent degradation of intracellular material. It aims to be the premier journal in the field and covers various connections between autophagy and human health and disease, such as cancer, neurodegeneration, aging, diabetes, myopathies, and heart disease. Autophagy is interested in all experimental systems, from yeast to human. Suggestions for specialized topics are welcome. The journal accepts the following types of articles: Original research, Reviews, Technical papers, Brief Reports, Addenda, Letters to the Editor, Commentaries and Views, and Articles on science and art. Autophagy is abstracted/indexed in Adis International Ltd (Reactions Weekly), EBSCOhost (Biological Abstracts), Elsevier BV (EMBASE and Scopus), PubMed, Biological Abstracts, Science Citation Index Expanded, Web of Science, and MEDLINE.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信