IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28874-9.html
   My bibliography  Save this article

Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress

Author

Listed:
  • Kihyoun Park

    (Yonsei University College of Medicine
    Sungkyunkwan University School of Medicine)

  • Hyejin Lim

    (Yonsei University College of Medicine)

  • Jinyoung Kim

    (Yonsei University College of Medicine)

  • Yeseong Hwang

    (Yonsei University College of Medicine)

  • Yu Seol Lee

    (Yonsei University College of Medicine)

  • Soo Han Bae

    (Yonsei University College of Medicine)

  • Hyeongseok Kim

    (Chungnam National University)

  • Hail Kim

    (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)

  • Shin-Wook Kang

    (Yonsei University College of Medicine)

  • Joo Young Kim

    (Department of Pharmacology and Brain Korea 21 Project for Medical Sciences)

  • Myung-Shik Lee

    (Yonsei University College of Medicine
    Yonsei University College of Medicine
    Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University)

Abstract

Although autophagy is critical for pancreatic β-cell function, the role and mechanism of mitophagy in β-cells are unclear. We studied the role of lysosomal Ca2+ in TFEB activation by mitochondrial or metabolic stress and that of TFEB-mediated mitophagy in β-cell function. Mitochondrial or metabolic stress induced mitophagy through lysosomal Ca2+ release, increased cytosolic Ca2+ and TFEB activation. Lysosomal Ca2+ replenishment by ER- > lysosome Ca2+ refilling was essential for mitophagy. β-cell-specific Tfeb knockout (TfebΔβ-cell) abrogated high-fat diet (HFD)-induced mitophagy, accompanied by increased ROS and reduced mitochondrial cytochrome c oxidase activity or O2 consumption. TfebΔβ-cell mice showed aggravation of HFD-induced glucose intolerance and impaired insulin release. Metabolic or mitochondrial stress induced TFEB-dependent expression of mitophagy receptors including Ndp52 and Optn, contributing to the increased mitophagy. These results suggest crucial roles of lysosomal Ca2+ release coupled with ER- > lysosome Ca2+ refilling and TFEB activation in mitophagy and maintenance of pancreatic β-cell function during metabolic stress.

Suggested Citation

  • Kihyoun Park & Hyejin Lim & Jinyoung Kim & Yeseong Hwang & Yu Seol Lee & Soo Han Bae & Hyeongseok Kim & Hail Kim & Shin-Wook Kang & Joo Young Kim & Myung-Shik Lee, 2022. "Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28874-9
    DOI: 10.1038/s41467-022-28874-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28874-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28874-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chulman Jo & Soner Gundemir & Susanne Pritchard & Youngnam N. Jin & Irfan Rahman & Gail V. W. Johnson, 2014. "Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    2. Xiaoli Zhang & Xiping Cheng & Lu Yu & Junsheng Yang & Raul Calvo & Samarjit Patnaik & Xin Hu & Qiong Gao & Meimei Yang & Maria Lawas & Markus Delling & Juan Marugan & Marc Ferrer & Haoxing Xu, 2016. "MCOLN1 is a ROS sensor in lysosomes that regulates autophagy," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    3. Junji Suzuki & Kazunori Kanemaru & Kuniaki Ishii & Masamichi Ohkura & Yohei Okubo & Masamitsu Iino, 2014. "Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    4. Michael Lazarou & Danielle A. Sliter & Lesley A. Kane & Shireen A. Sarraf & Chunxin Wang & Jonathon L. Burman & Dionisia P. Sideris & Adam I. Fogel & Richard J. Youle, 2015. "The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy," Nature, Nature, vol. 524(7565), pages 309-314, August.
    5. Dongbiao Shen & Xiang Wang & Xinran Li & Xiaoli Zhang & Zepeng Yao & Shannon Dibble & Xian-ping Dong & Ting Yu & Andrew P. Lieberman & Hollis D. Showalter & Haoxing Xu, 2012. "Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    6. Xin Li & Guangyan Wu & Yin Yang & Shijuan Fu & Xiaofen Liu & Huimin Kang & Xue Yang & Xun-Cheng Su & Yuequan Shen, 2017. "Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    7. Jinyoung Kim & Kihyoun Park & Min Jung Kim & Hyejin Lim & Kook Hwan Kim & Sun-Woo Kim & Eun-Seo Lee & Hyongbum (Henry) Kim & Sung Joo Kim & Kyu Yeon Hur & Jae Hyeon Kim & Jin Hee Ahn & Kun-Ho Yoon & J, 2021. "An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Dengqin Zhong & Ruiyun Wang & Hongjing Zhang & Mengmeng Wang & Xuxia Zhang & Honghong Chen, 2023. "Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Ara Lee & Gihyun Sung & Sanghee Shin & Song-Yi Lee & Jaehwan Sim & Truong Thi My Nhung & Tran Diem Nghi & Sang Ki Park & Ponnusamy Pon Sathieshkumar & Imkyeung Kang & Ji Young Mun & Jong-Seo Kim & Hyu, 2024. "OrthoID: profiling dynamic proteomes through time and space using mutually orthogonal chemical tools," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Flavia Giamogante & Lucia Barazzuol & Francesca Maiorca & Elena Poggio & Alessandra Esposito & Anna Masato & Gennaro Napolitano & Alessio Vagnoni & Tito Calì & Marisa Brini, 2024. "A SPLICS reporter reveals $${{{{{\boldsymbol{\alpha }}}}}}$$ α -synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Thanh-an Pham & Aleix Boquet-Pujadas & Sandip Mondal & Michael Unser & George Barbastathis, 2024. "Deep-prior ODEs augment fluorescence imaging with chemical sensors," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Kyla Germain & Raphaella W. L. So & Laura F. DiGiovanni & Joel C. Watts & Robert H. J. Bandsma & Peter K. Kim, 2024. "Upregulated pexophagy limits the capacity of selective autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Paloma García Casas & Michela Rossini & Linnea Påvénius & Mezida Saeed & Nikita Arnst & Sonia Sonda & Tânia Fernandes & Irene D’Arsiè & Matteo Bruzzone & Valeria Berno & Andrea Raimondi & Maria Livia , 2024. "Simultaneous detection of membrane contact dynamics and associated Ca2+ signals by reversible chemogenetic reporters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    7. Taeko Sasaki & Yasuharu Kushida & Takuya Norizuki & Hidetaka Kosako & Ken Sato & Miyuki Sato, 2024. "ALLO-1- and IKKE-1-dependent positive feedback mechanism promotes the initiation of paternal mitochondrial autophagy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Yoshito Minami & Atsushi Hoshino & Yusuke Higuchi & Masahide Hamaguchi & Yusaku Kaneko & Yuhei Kirita & Shunta Taminishi & Toshiyuki Nishiji & Akiyuki Taruno & Michiaki Fukui & Zoltan Arany & Satoaki , 2023. "Liver lipophagy ameliorates nonalcoholic steatohepatitis through extracellular lipid secretion," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Shuang-zhou Peng & Xiao-hui Chen & Si-jie Chen & Jie Zhang & Chuan-ying Wang & Wei-rong Liu & Duo Zhang & Ying Su & Xiao-kun Zhang, 2021. "Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    10. Eunbyul Cho & Youngsik Woo & Yeongjun Suh & Bo Kyoung Suh & Soo Jeong Kim & Truong Thi My Nhung & Jin Yeong Yoo & Tran Diem Nghi & Su Been Lee & Dong Jin Mun & Sang Ki Park, 2023. "Ratiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Qiang Zhu & Matthew E. Combs & Juan Liu & Xue Bai & Wenbo B. Wang & Laura E. Herring & Jiandong Liu & Jason W. Locasale & Dawn E. Bowles & Ryan T. Gross & Michelle Mendiola Pla & Christopher P. Mack &, 2023. "GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    12. Iqbal Dulloo & Peace Atakpa-Adaji & Yi-Chun Yeh & Clémence Levet & Sonia Muliyil & Fangfang Lu & Colin W. Taylor & Matthew Freeman, 2022. "iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    13. Su Jin Ham & Heesuk Yoo & Daihn Woo & Da Hyun Lee & Kyu-Sang Park & Jongkyeong Chung, 2023. "PINK1 and Parkin regulate IP3R-mediated ER calcium release," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Fumika Koyano & Koji Yamano & Tomoyuki Hoshina & Hidetaka Kosako & Yukio Fujiki & Keiji Tanaka & Noriyuki Matsuda, 2024. "AAA+ ATPase chaperone p97/VCPFAF2 governs basal pexophagy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Roman Nikolaienko & Elisa Bovo & Daniel Kahn & Ryan Gracia & Thomas Jamrozik & Aleksey V. Zima, 2023. "Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR)," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    16. Remzi Onur Eren & Göksu Gökberk Kaya & Robin Schwarzer & Manolis Pasparakis, 2024. "IKKε and TBK1 prevent RIPK1 dependent and independent inflammation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    17. Wenhao Li & Hongwei Zhu & Jinzhu Chen & Binglu Ru & Qin Peng & Jianqiang Miao & Xili Liu, 2024. "PsAF5 functions as an essential adapter for PsPHB2-mediated mitophagy under ROS stress in Phytophthora sojae," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Huan Yang & Caroline Sibilla & Raymond Liu & Jina Yun & Bruce A. Hay & Craig Blackstone & David C. Chan & Robert J. Harvey & Ming Guo, 2022. "Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    19. Shuai Gao & Lingyu Gao & Dailin Yuan & Xu’ai Lin & Stijn Veen, 2024. "Gonococcal OMV-delivered PorB induces epithelial cell mitophagy," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    20. Zhen Yuan & Kun Cai & Jiajia Li & Ruifeng Chen & Fuhai Zhang & Xuan Tan & Yaming Jiu & Haishuang Chang & Bing Hu & Weiyi Zhang & Binbin Ding, 2024. "ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28874-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.