IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26331-7.html
   My bibliography  Save this article

GAK and PRKCD are positive regulators of PRKN-independent mitophagy

Author

Listed:
  • Michael J. Munson

    (University of Oslo
    University of Oslo
    BioPharmaceuticals R&D, AstraZeneca)

  • Benan J. Mathai

    (University of Oslo
    University of Oslo)

  • Matthew Yoke Wui Ng

    (University of Oslo
    University of Oslo)

  • Laura Trachsel-Moncho

    (University of Oslo
    University of Oslo)

  • Laura R. Ballina

    (University of Oslo
    University of Oslo)

  • Sebastian W. Schultz

    (University of Oslo
    The Norwegian Radium Hospital Montebello)

  • Yahyah Aman

    (University of Oslo and Akershus University Hospital)

  • Alf H. Lystad

    (University of Oslo
    University of Oslo)

  • Sakshi Singh

    (University of Oslo
    University of Oslo)

  • Sachin Singh

    (University of Oslo
    The Norwegian Radium Hospital Montebello)

  • Jørgen Wesche

    (University of Oslo
    The Norwegian Radium Hospital Montebello)

  • Evandro F. Fang

    (University of Oslo and Akershus University Hospital)

  • Anne Simonsen

    (University of Oslo
    University of Oslo
    The Norwegian Radium Hospital Montebello)

Abstract

The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators of PRKN-independent mitophagy using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as regulators of PRKN-independent mitophagy, with both being dispensable for PRKN-dependent mitophagy and starvation-induced autophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagy in vitro, that PRKCD is present on mitochondria, and that PRKCD facilitates recruitment of ULK1/ATG13 to early autophagic structures. Importantly, we demonstrate in vivo relevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (gakh-1) in C. elegans or knockout of PRKCD homologues in zebrafish led to significant inhibition of basal mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy regulation.

Suggested Citation

  • Michael J. Munson & Benan J. Mathai & Matthew Yoke Wui Ng & Laura Trachsel-Moncho & Laura R. Ballina & Sebastian W. Schultz & Yahyah Aman & Alf H. Lystad & Sakshi Singh & Sachin Singh & Jørgen Wesche , 2021. "GAK and PRKCD are positive regulators of PRKN-independent mitophagy," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26331-7
    DOI: 10.1038/s41467-021-26331-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26331-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26331-7?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. Konstantinos Palikaras & Eirini Lionaki & Nektarios Tavernarakis, 2015. "Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans," Nature, Nature, vol. 521(7553), pages 525-528, May.
    2. Petter Holland & Helene Knævelsrud & Kristiane Søreng & Benan J. Mathai & Alf Håkon Lystad & Serhiy Pankiv & Gunnveig T. Bjørndal & Sebastian W. Schultz & Viola H. Lobert & Robin B. Chan & Bowen Zhou , 2016. "HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    3. 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.
    4. Matthew Y. Tang & Marta Vranas & Andrea I. Krahn & Shayal Pundlik & Jean- François Trempe & Edward A. Fon, 2017. "Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    Full references (including those not matched with items on IDEAS)

    Citations

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


    Cited by:

    1. Matthew Yoke Wui Ng & Chara Charsou & Ana Lapao & Sakshi Singh & Laura Trachsel-Moncho & Sebastian W. Schultz & Sigve Nakken & Michael J. Munson & Anne Simonsen, 2022. "The cholesterol transport protein GRAMD1C regulates autophagy initiation and mitochondrial bioenergetics," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. Paula P. Coelho & Geoffrey G. Hesketh & Annika Pedersen & Elena Kuzmin & Anne-Marie N. Fortier & Emily S. Bell & Colin D. H. Ratcliffe & Anne-Claude Gingras & Morag Park, 2022. "Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. 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.
    7. 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.
    8. Keisuke Tabata & Vibhu Prasad & David Paul & Ji-Young Lee & Minh-Tu Pham & Woan-Ing Twu & Christopher J. Neufeldt & Mirko Cortese & Berati Cerikan & Yannick Stahl & Sebastian Joecks & Cong Si Tran & C, 2021. "Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    9. Eirini Lionaki & Ilias Gkikas & Ioanna Daskalaki & Maria-Konstantina Ioannidi & Maria I. Klapa & Nektarios Tavernarakis, 2022. "Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
    14. Michael Webb & Jyoti Malhotra & Chui-Se Tham & Matthew Goddeeris & Douglas W McMillin & Effie Tozzo, 2017. "A Novel Mitophagy Assay for Skeletal Myotubes," Open Access Journal of Neurology & Neurosurgery, Juniper Publishers Inc., vol. 4(4), pages 79-86, July.
    15. Hayden Weng Siong Tan & Guang Lu & Han Dong & Yik-Lam Cho & Auginia Natalia & Liming Wang & Charlene Chan & Dennis Kappei & Reshma Taneja & Shuo-Chien Ling & Huilin Shao & Shih-Yin Tsai & Wen-Xing Din, 2022. "A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    16. Simon Maria Kienle & Tobias Schneider & Katrin Stuber & Christoph Globisch & Jasmin Jansen & Florian Stengel & Christine Peter & Andreas Marx & Michael Kovermann & Martin Scheffner, 2022. "Electrostatic and steric effects underlie acetylation-induced changes in ubiquitin structure and function," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Morgane Mabire & Pushpa Hegde & Adel Hammoutene & Jinghong Wan & Charles Caër & Rola Al Sayegh & Mathilde Cadoux & Manon Allaire & Emmanuel Weiss & Tristan Thibault-Sogorb & Olivier Lantz & Michèle Go, 2023. "MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:12:y:2021:i:1:d:10.1038_s41467-021-26331-7. 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.