IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50222-2.html
   My bibliography  Save this article

Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes

Author

Listed:
  • Kazuhiro Yamada

    (University of Pittsburgh
    Osaka Metropolitan University)

  • Claudette Croix

    (University of Pittsburgh)

  • Donna B. Stolz

    (University of Pittsburgh)

  • Yulia Y. Tyurina

    (University of Pittsburgh)

  • Vladimir A. Tyurin

    (University of Pittsburgh)

  • Laura R. Bradley

    (University of Pittsburgh)

  • Alexander A. Kapralov

    (University of Pittsburgh)

  • Yanhan Deng

    (University of Pittsburgh
    Huazhong University of Science and Technology)

  • Xiuxia Zhou

    (University of Pittsburgh)

  • Qi Wei

    (University of Pittsburgh)

  • Bo Liao

    (University of Pittsburgh
    Huazhong University of Science and Technology)

  • Nobuhiko Fukuda

    (University of Pittsburgh
    Yokohama City University Graduate School of Medicine)

  • Mara Sullivan

    (University of Pittsburgh)

  • John Trudeau

    (University of Pittsburgh)

  • Anuradha Ray

    (University of Pittsburgh)

  • Valerian E. Kagan

    (University of Pittsburgh)

  • Jinming Zhao

    (University of Pittsburgh)

  • Sally E. Wenzel

    (University of Pittsburgh)

Abstract

A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)−1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.

Suggested Citation

  • Kazuhiro Yamada & Claudette Croix & Donna B. Stolz & Yulia Y. Tyurina & Vladimir A. Tyurin & Laura R. Bradley & Alexander A. Kapralov & Yanhan Deng & Xiuxia Zhou & Qi Wei & Bo Liao & Nobuhiko Fukuda &, 2024. "Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50222-2
    DOI: 10.1038/s41467-024-50222-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50222-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50222-2?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. 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.
    2. Klaus van Leyen & Robert M. Duvoisin & Harald Engelhardt & Martin Wiedmann, 1998. "A function for lipoxygenase in programmed organelle degradation," Nature, Nature, vol. 395(6700), pages 392-395, September.
    3. Chao Mao & Xiaoguang Liu & Yilei Zhang & Guang Lei & Yuelong Yan & Hyemin Lee & Pranavi Koppula & Shiqi Wu & Li Zhuang & Bingliang Fang & Masha V. Poyurovsky & Kellen Olszewski & Boyi Gan, 2021. "Author Correction: DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer," Nature, Nature, vol. 596(7873), pages 13-13, August.
    4. Chao Mao & Xiaoguang Liu & Yilei Zhang & Guang Lei & Yuelong Yan & Hyemin Lee & Pranavi Koppula & Shiqi Wu & Li Zhuang & Bingliang Fang & Masha V. Poyurovsky & Kellen Olszewski & Boyi Gan, 2021. "DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer," Nature, Nature, vol. 593(7860), pages 586-590, May.
    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. Bin Huang & Hui Wang & Shuo Liu & Meng Hao & Dan Luo & Yi Zhou & Ying Huang & Yong Nian & Lei Zhang & Bo Chu & Chengqian Yin, 2025. "Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    2. Yandi Wu & Tongsheng Huang & Xinghui Li & Conghui Shen & Honglin Ren & Haiping Wang & Teng Wu & Xinlu Fu & Shijie Deng & Ziqi Feng & Shijie Xiong & Hui Li & Saifei Gao & Zhenyu Yang & Fei Gao & Lele D, 2023. "Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. Dong Liu & Hannah C. Webber & Fuyun Bian & Yangfan Xu & Manjari Prakash & Xue Feng & Ming Yang & Hang Yang & In-Jee You & Liang Li & Liping Liu & Pingting Liu & Haoliang Huang & Chien-Yi Chang & Liang, 2025. "Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    9. Dadi Jiang & Youming Guo & Tianyu Wang & Liang Wang & Yuelong Yan & Ling Xia & Rakesh Bam & Zhifen Yang & Hyemin Lee & Takao Iwawaki & Boyi Gan & Albert C. Koong, 2024. "IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Pranavi Koppula & Guang Lei & Yilei Zhang & Yuelong Yan & Chao Mao & Lavanya Kondiparthi & Jiejun Shi & Xiaoguang Liu & Amber Horbath & Molina Das & Wei Li & Masha V. Poyurovsky & Kellen Olszewski & B, 2022. "A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. 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.
    12. 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.
    13. Na Yeon Park & Doo Sin Jo & Jae-Yoon Yang & Ji-Eun Bae & Joon Bum Kim & Yong Hwan Kim & Seong Hyun Kim & Pansoo Kim & Dong-Seok Lee & Tamotsu Yoshimori & Eun-Kyeong Jo & Eunbyul Yeom & Dong-Hyung Cho, 2025. "Activation of lysophagy by a TBK1-SCFFBXO3-TMEM192-TAX1BP1 axis in response to lysosomal damage," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    14. Mihee Oh & Seo Young Jang & Ji-Yoon Lee & Jong Woo Kim & Youngae Jung & Jiwoo Kim & Jinho Seo & Tae-Su Han & Eunji Jang & Hye Young Son & Dain Kim & Min Wook Kim & Jin-Sung Park & Kwon-Ho Song & Kyoun, 2023. "The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. M. T. Herrera-Abreu & J. Guan & U. Khalid & J. Ning & M. R. Costa & J. Chan & Q. Li & J-P. Fortin & W. R. Wong & P. Perampalam & A. Biton & W. Sandoval & J. Vijay & M. Hafner & R. Cutts & G. Wilson & , 2024. "Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    16. 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.
    17. Jie Zhang & Suning Liu & Yang Li & Guanfeng Xu & Huimin Deng & Kirst King-Jones & Sheng Li, 2025. "Nutrient status alters developmental fates via a switch in mitochondrial homeodynamics," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    18. Guoshu Bi & Jiaqi Liang & Yunyi Bian & Guangyao Shan & Yiwei Huang & Tao Lu & Huan Zhang & Xing Jin & Zhencong Chen & Mengnan Zhao & Hong Fan & Qun Wang & Boyi Gan & Cheng Zhan, 2024. "Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. Yuelong Yan & Hongqi Teng & Qinglei Hang & Lavanya Kondiparthi & Guang Lei & Amber Horbath & Xiaoguang Liu & Chao Mao & Shiqi Wu & Li Zhuang & M. James You & Masha V. Poyurovsky & Li Ma & Kellen Olsze, 2023. "SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Wei Yang & Bo Mu & Jing You & Chenyu Tian & Huachao Bin & Zhiqiang Xu & Liting Zhang & Ronggang Ma & Ming Wu & Guo Zhang & Chong Huang & Linli Li & Zhenhua Shao & Lunzhi Dai & Laurent Désaubry & Sheng, 2022. "Non-classical ferroptosis inhibition by a small molecule targeting PHB2," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:15:y:2024:i:1:d:10.1038_s41467-024-50222-2. 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.