IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v458y2009i7242d10.1038_nature07976.html
   My bibliography  Save this article

Autophagy regulates lipid metabolism

Author

Listed:
  • Rajat Singh

    (Department of Medicine,
    The Marion Bessin Liver Research Center,)

  • Susmita Kaushik

    (Department of Medicine,
    The Marion Bessin Liver Research Center,
    Department of Developmental and Molecular Biology,
    Institute for Aging Studies,)

  • Yongjun Wang

    (Department of Medicine,
    The Marion Bessin Liver Research Center,)

  • Youqing Xiang

    (Department of Medicine,
    The Marion Bessin Liver Research Center,)

  • Inna Novak

    (The Marion Bessin Liver Research Center,
    Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA)

  • Masaaki Komatsu

    (Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan)

  • Keiji Tanaka

    (Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan)

  • Ana Maria Cuervo

    (Department of Medicine,
    The Marion Bessin Liver Research Center,
    Department of Developmental and Molecular Biology,
    Institute for Aging Studies,)

  • Mark J. Czaja

    (Department of Medicine,
    The Marion Bessin Liver Research Center,)

Abstract

The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.

Suggested Citation

  • Rajat Singh & Susmita Kaushik & Yongjun Wang & Youqing Xiang & Inna Novak & Masaaki Komatsu & Keiji Tanaka & Ana Maria Cuervo & Mark J. Czaja, 2009. "Autophagy regulates lipid metabolism," Nature, Nature, vol. 458(7242), pages 1131-1135, April.
    • Handle: RePEc:nat:nature:v:458:y:2009:i:7242:d:10.1038_nature07976
    DOI: 10.1038/nature07976
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature07976
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature07976?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Donghai Cui & Zixiang Wang & Qianli Dang & Jing Wang & Junchao Qin & Jianping Song & Xiangyu Zhai & Yachao Zhou & Ling Zhao & Gang Lu & Hongbin Liu & Gang Liu & Runping Liu & Changshun Shao & Xiyu Zha, 2023. "Spliceosome component Usp39 contributes to hepatic lipid homeostasis through the regulation of autophagy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. 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.
    3. Xiaowei Sun & Jie Shen & Norbert Perrimon & Xue Kong & Dan Wang, 2023. "The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. 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.
    5. Elodie Mailler & Carlos M. Guardia & Xiaofei Bai & Michal Jarnik & Chad D. Williamson & Yan Li & Nunziata Maio & Andy Golden & Juan S. Bonifacino, 2021. "The autophagy protein ATG9A enables lipid mobilization from lipid droplets," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    6. Yahui Li & Chunyan Li & Chenchen Zhao & Jiayu Wu & Ya Zhu & Fei Wang & Jiepeng Zhong & Yan Yan & Yulan Jin & Weiren Dong & Jinyang Chen & Xianghong Yang & Jiyong Zhou & Boli Hu, 2024. "Coronavirus M protein promotes mitophagy over virophagy by recruiting PDPK1 to phosphorylate SQSTM1 at T138," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Lin-lin Zhao & Ru Chen & Ziyu Bai & Junyi Liu & Yuhao Zhang & Yicheng Zhong & Meng-xiang Sun & Peng Zhao, 2024. "Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Hong Huang & Qinqin Ouyang & Min Zhu & Haijia Yu & Kunrong Mei & Rong Liu, 2021. "mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    9. Wenjun Wang & Junyang Tan & Xiaomin Liu & Wenqi Guo & Mengmeng Li & Xinjie Liu & Yanyan Liu & Wenyu Dai & Liubing Hu & Yimin Wang & Qiuxia Lu & Wen Xing Lee & Hong-Wen Tang & Qinghua Zhou, 2023. "Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Youping Lin & Haixu Chen & Lei Wang & Jiaojiao Su & Junbo Li & Xin Huang, 2024. "Lipase activated endocytosis-like behavior of oil-in-water emulsion," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Jialiu Zeng & Rebeca Acin-Perez & Essam A. Assali & Andrew Martin & Alexandra J. Brownstein & Anton Petcherski & Lucía Fernández-del-Rio & Ruiqing Xiao & Chih Hung Lo & Michaël Shum & Marc Liesa & Xue, 2023. "Restoration of lysosomal acidification rescues autophagy and metabolic dysfunction in non-alcoholic fatty liver disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. King Hang Tommy Mau & Donja Karimlou & David Barneda & Vincent Brochard & Christophe Royer & Bryony Leeke & Roshni A. Souza & Mélanie Pailles & Michelle Percharde & Shankar Srinivas & Alice Jouneau & , 2022. "Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    13. Keiji Kajiwara & Hiroshi Osaki & Steffen Greßies & Keiko Kuwata & Ju Hyun Kim & Tobias Gensch & Yoshikatsu Sato & Frank Glorius & Shigehiro Yamaguchi & Masayasu Taki, 2022. "A negative-solvatochromic fluorescent probe for visualizing intracellular distributions of fatty acid metabolites," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Zhenzhen Zi & Zhuzhen Zhang & Qiang Feng & Chiho Kim & Xu-Dong Wang & Philipp E. Scherer & Jinming Gao & Beth Levine & Yonghao Yu, 2022. "Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Yun Seok Kim & Bongsub Ko & Da Jung Kim & Jihoon Tak & Chang Yeob Han & Joo-Youn Cho & Won Kim & Sang Geon Kim, 2022. "Induction of the hepatic aryl hydrocarbon receptor by alcohol dysregulates autophagy and phospholipid metabolism via PPP2R2D," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Scotland E. Farley & Jennifer E. Kyle & Hans C. Leier & Lisa M. Bramer & Jules B. Weinstein & Timothy A. Bates & Joon-Yong Lee & Thomas O. Metz & Carsten Schultz & Fikadu G. Tafesse, 2022. "A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Leslie A. Rowland & Adilson Guilherme & Felipe Henriques & Chloe DiMarzio & Sean Munroe & Nicole Wetoska & Mark Kelly & Keith Reddig & Gregory Hendricks & Meixia Pan & Xianlin Han & Olga R. Ilkayeva &, 2023. "De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Guanlan Hu & Catriona Ling & Lijun Chi & Mehakpreet K. Thind & Samuel Furse & Albert Koulman & Jonathan R. Swann & Dorothy Lee & Marjolein M. Calon & Celine Bourdon & Christian J. Versloot & Barbara M, 2022. "The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Odeta Meçe & Diede Houbaert & Maria-Livia Sassano & Tania Durré & Hannelore Maes & Marco Schaaf & Sanket More & Maarten Ganne & Melissa García-Caballero & Mila Borri & Jelle Verhoeven & Madhur Agrawal, 2022. "Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    20. Denisa Margină & Anca Ungurianu & Carmen Purdel & Dimitris Tsoukalas & Evangelia Sarandi & Maria Thanasoula & Fotios Tekos & Robin Mesnage & Demetrios Kouretas & Aristidis Tsatsakis, 2020. "Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors," IJERPH, MDPI, vol. 17(11), pages 1-27, June.
    21. Hejazi Keyvan & Fathi Mehrdad & Salkhord Mahsa & Dastani Maryam, 2021. "The Effect of Eight Weeks of Combined Training (Endurance-Intermittent Resistance and Endurance-Continuous Resistance) on Coagulation, Fibrinolytic and Lipid Profiles of Overweight Women," Polish Journal of Sport and Tourism, Sciendo, vol. 28(4), pages 3-9, 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:nature:v:458:y:2009:i:7242:d:10.1038_nature07976. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.