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Intracristal space proteome mapping using super-resolution proximity labeling with isotope-coded probes

Author

Listed:
  • Myeong-Gyun Kang

    (Seoul National University)

  • Sanghee Shin

    (Seoul National University
    Seoul National University
    Dana-Farber Cancer Institute)

  • Dong-Gi Jang

    (Seoul National University
    Institute for Basic Science)

  • Ohyeon Kwon

    (Ulsan National Institute of Science and Technology (UNIST))

  • Song-Yi Lee

    (Seoul National University
    Daegu Gyeongbuk Institute of Science & Technology (DGIST)
    Daegu Gyeongbuk Institute of Science & Technology (DGIST))

  • Pratyush Kumar Mishra

    (Seoul National University)

  • Minkyo Jung

    (Korea Brain Research Institute)

  • Ji Young Mun

    (Korea Brain Research Institute)

  • Jung-Min Kee

    (Ulsan National Institute of Science and Technology (UNIST))

  • Jong-Seo Kim

    (Seoul National University
    Institute for Basic Science)

  • Hyun-Woo Rhee

    (Seoul National University
    Seoul National University)

Abstract

Proximity labeling with engineered ascorbate peroxidase (APEX) has been widely used to identify proteomes within various membrane-enclosed subcellular organelles. However, constructing protein distribution maps between two non-partitioned proximal spaces remains challenging with the current proximity labeling tools. Here, we introduce a proximity labeling approach using isotope-coded phenol probes for APEX labeling (ICAX) that enables the quantitative analysis of the spatial proteome at nanometer resolution between two distinctly localized APEX enzymes. Using this technique, we identify the spatial proteomic architecture of the mitochondrial intracristal space (ICS), which is not physically separated from the peripheral space. ICAX analysis further reveals unexpected dynamics of the mitochondrial spatiome under mitochondrial contact site and cristae organizing system (MICOS) complex inhibition and mitochondrial uncoupling, respectively. Overall, these findings highlight the importance of ICS for mitochondrial quality control under dynamic stress conditions.

Suggested Citation

  • Myeong-Gyun Kang & Sanghee Shin & Dong-Gi Jang & Ohyeon Kwon & Song-Yi Lee & Pratyush Kumar Mishra & Minkyo Jung & Ji Young Mun & Jung-Min Kee & Jong-Seo Kim & Hyun-Woo Rhee, 2025. "Intracristal space proteome mapping using super-resolution proximity labeling with isotope-coded probes," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62756-0
    DOI: 10.1038/s41467-025-62756-0
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    References listed on IDEAS

    as
    1. Ciaran P. Seath & Antony J. Burton & Xuemeng Sun & Gihoon Lee & Ralph E. Kleiner & David W. C. MacMillan & Tom W. Muir, 2023. "Tracking chromatin state changes using nanoscale photo-proximity labelling," Nature, Nature, vol. 616(7957), pages 574-580, April.
    2. Fu Zheng & Chenxin Yu & Xinyue Zhou & Peng Zou, 2023. "Publisher Correction: Genetically encoded photocatalytic protein labeling enables spatially-resolved profiling of intracellular proteome," Nature Communications, Nature, vol. 14(1), pages 1-1, December.
    3. Wei Qin & Samuel A. Myers & Dominique K. Carey & Steven A. Carr & Alice Y. Ting, 2021. "Spatiotemporally-resolved mapping of RNA binding proteins via functional proximity labeling reveals a mitochondrial mRNA anchor promoting stress recovery," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    4. Fu Zheng & Chenxin Yu & Xinyue Zhou & Peng Zou, 2023. "Genetically encoded photocatalytic protein labeling enables spatially-resolved profiling of intracellular proteome," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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