IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39820-8.html
   My bibliography  Save this article

Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle

Author

Listed:
  • Paul T. Morse

    (Wayne State University)

  • Gonzalo Pérez-Mejías

    (Universidad de Sevilla - CSIC)

  • Junmei Wan

    (Wayne State University)

  • Alice A. Turner

    (Wayne State University
    Wayne State University)

  • Inmaculada Márquez

    (Universidad de Sevilla - CSIC)

  • Hasini A. Kalpage

    (Wayne State University)

  • Asmita Vaishnav

    (Wayne State University)

  • Matthew P. Zurek

    (Wayne State University
    Wayne State University)

  • Philipp P. Huettemann

    (Wayne State University)

  • Katherine Kim

    (Wayne State University)

  • Tasnim Arroum

    (Wayne State University)

  • Miguel A. Rosa

    (Universidad de Sevilla - CSIC)

  • Dipanwita Dutta Chowdhury

    (Wayne State University)

  • Icksoo Lee

    (Dankook University)

  • Joseph S. Brunzelle

    (Northwestern University, Center for Synchrotron Research)

  • Thomas H. Sanderson

    (University of Michigan Medical School)

  • Moh H. Malek

    (Wayne State University)

  • David Meierhofer

    (Max Planck Institute for Molecular Genetics)

  • Brian F. P. Edwards

    (Wayne State University)

  • Irene Díaz-Moreno

    (Universidad de Sevilla - CSIC)

  • Maik Hüttemann

    (Wayne State University
    Wayne State University)

Abstract

Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc (1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.

Suggested Citation

  • Paul T. Morse & Gonzalo Pérez-Mejías & Junmei Wan & Alice A. Turner & Inmaculada Márquez & Hasini A. Kalpage & Asmita Vaishnav & Matthew P. Zurek & Philipp P. Huettemann & Katherine Kim & Tasnim Arrou, 2023. "Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39820-8
    DOI: 10.1038/s41467-023-39820-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39820-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39820-8?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. Alan K. Okada & Kazuki Teranishi & Mark R. Ambroso & Jose Mario Isas & Elena Vazquez-Sarandeses & Joo-Yeun Lee & Arthur Alves Melo & Priyatama Pandey & Daniel Merken & Leona Berndt & Michael Lammers &, 2021. "Lysine acetylation regulates the interaction between proteins and membranes," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Cuihong Wan & Blake Borgeson & Sadhna Phanse & Fan Tu & Kevin Drew & Greg Clark & Xuejian Xiong & Olga Kagan & Julian Kwan & Alexandr Bezginov & Kyle Chessman & Swati Pal & Graham Cromar & Ophelia Pap, 2015. "Panorama of ancient metazoan macromolecular complexes," Nature, Nature, vol. 525(7569), pages 339-344, September.
    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. Yuwan Chen & Wen Zhou & Yufei Xia & Weijie Zhang & Qun Zhao & Xinwei Li & Hang Gao & Zhen Liang & Guanghui Ma & Kaiguang Yang & Lihua Zhang & Yukui Zhang, 2023. "Targeted cross-linker delivery for the in situ mapping of protein conformations and interactions in mitochondria," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Krishna B. S. Swamy & Hsin-Yi Lee & Carmina Ladra & Chien-Fu Jeff Liu & Jung-Chi Chao & Yi-Yun Chen & Jun-Yi Leu, 2022. "Proteotoxicity caused by perturbed protein complexes underlies hybrid incompatibility in yeast," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Nilesh Kumar & M. Shahid Mukhtar, 2024. "Viral Targets in the Human Interactome with Comprehensive Centrality Analysis: SARS-CoV-2, a Case Study," Data, MDPI, vol. 9(8), pages 1-12, August.
    4. Jingyun Quan & Xiaoxia Wen & Guomei Su & Yu Zhong & Tong Huang & Zhilin Xiong & Jiewen Huang & Yingying Lv & Shihai Li & Shuhua Luo & Chaole Luo & Xin Cai & Xianwen Lai & Yuanyuan Xiang & Song Guo Zhe, 2023. "Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Pierre C. Havugimana & Raghuveera Kumar Goel & Sadhna Phanse & Ahmed Youssef & Dzmitry Padhorny & Sergei Kotelnikov & Dima Kozakov & Andrew Emili, 2022. "Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    6. Chuan Qin & Leonie G. Graf & Kilian Striska & Markus Janetzky & Norman Geist & Robin Specht & Sabrina Schulze & Gottfried J. Palm & Britta Girbardt & Babett Dörre & Leona Berndt & Stefan Kemnitz & Mar, 2024. "Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    7. Sandhya Malla & Kanchan Kumari & Carlos A. García-Prieto & Jonatan Caroli & Anna Nordin & Trinh T. T. Phan & Devi Prasad Bhattarai & Carlos Martinez-Gamero & Eshagh Dorafshan & Stephanie Stransky & Da, 2024. "The scaffolding function of LSD1 controls DNA methylation in mouse ESCs," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    8. Michael A. Skinnider & Mopelola O. Akinlaja & Leonard J. Foster, 2023. "Mapping protein states and interactions across the tree of life with co-fractionation mass spectrometry," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Hélène Bret & Jinmei Gao & Diego Javier Zea & Jessica Andreani & Raphaël Guerois, 2024. "From interaction networks to interfaces, scanning intrinsically disordered regions using AlphaFold2," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. 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.

    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:14:y:2023:i:1:d:10.1038_s41467-023-39820-8. 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.