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    A Genetically Encoded FRET Sensor for Intracellular Heme
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    † Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
    ‡ Department of Chemistry and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, United States
    § Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China
    ∥ Peking-Tinghua Center for Life Sciences, Beijing, China
    ⊥ State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
    # Shanghai Universities E-Institute for Chemical Biology, Shanghai, China
    *E-mail: [email protected]
    *E-mail: [email protected]
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    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2015, 10, 7, 1610–1615
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    https://doi.org/10.1021/cb5009734
    Published April 10, 2015
    Copyright © 2015 American Chemical Society
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    Abstract

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    Heme plays pivotal roles in various cellular processes as well as in iron homeostasis in living systems. Here, we report a genetically encoded fluorescence resonance energy transfer (FRET) sensor for selective heme imaging by employing a pair of bacterial heme transfer chaperones as the sensory components. This heme-specific probe allows spatial-temporal visualization of intracellular heme distribution within living cells.

    Copyright © 2015 American Chemical Society

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    3. Wenyue Cao, Chia-Chuan Dean Cho, Zhi Zachary Geng, Namir Shaabani, Xinyu R. Ma, Erol C. Vatansever, Yugendar R. Alugubelli, Yuying Ma, Sankar P. Chaki, William H. Ellenburg, Kai S. Yang, Yuchen Qiao, Robert Allen, Benjamin W. Neuman, Henry Ji, Shiqing Xu, Wenshe Ray Liu. Evaluation of SARS-CoV-2 Main Protease Inhibitors Using a Novel Cell-Based Assay. ACS Central Science 2022, 8 (2) , 192-204. https://doi.org/10.1021/acscentsci.1c00910
    4. Andrea E. Gallio, Simon S.-P. Fung, Ana Cammack-Najera, Andrew J. Hudson, Emma L. Raven. Understanding the Logistics for the Distribution of Heme in Cells. JACS Au 2021, 1 (10) , 1541-1555. https://doi.org/10.1021/jacsau.1c00288
    5. Edward R. H. Walter, Ying Ge, Justin C. Mason, Joseph J. Boyle, Nicholas J. Long. A Coumarin–Porphyrin FRET Break-Apart Probe for Heme Oxygenase-1. Journal of the American Chemical Society 2021, 143 (17) , 6460-6469. https://doi.org/10.1021/jacs.0c12864
    6. Shuai Xu, Hong-Wen Liu, Lanlan Chen, Jie Yuan, Yongchao Liu, Lili Teng, Shuang-Yan Huan, Lin Yuan, Xiao-Bing Zhang, Weihong Tan. Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems. Journal of the American Chemical Society 2020, 142 (5) , 2129-2133. https://doi.org/10.1021/jacs.9b11245
    7. Samaneh Dastpeyman, Robert Godin, Gonzalo Cosa, Ann M. English. Quantifying Heme–Protein Maturation from Ratiometric Fluorescence Lifetime Measurements on the Single Fluorophore in Its GFP Fusion. The Journal of Physical Chemistry A 2020, 124 (4) , 746-754. https://doi.org/10.1021/acs.jpca.9b11901
    8. Eric C. Greenwald, Sohum Mehta, Jin Zhang. Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks. Chemical Reviews 2018, 118 (24) , 11707-11794. https://doi.org/10.1021/acs.chemrev.8b00333
    9. Sheng Wang, Miao Ding, Boxin Xue, Yingping Hou, Yujie Sun. Live Cell Visualization of Multiple Protein–Protein Interactions with BiFC Rainbow. ACS Chemical Biology 2018, 13 (5) , 1180-1188. https://doi.org/10.1021/acschembio.7b00931
    10. Andy Jing Chen, Xiaojing Yuan, Junjie Li, Puting Dong, Iqbal Hamza, Ji-Xin Cheng. Label-Free Imaging of Heme Dynamics in Living Organisms by Transient Absorption Microscopy. Analytical Chemistry 2018, 90 (5) , 3395-3401. https://doi.org/10.1021/acs.analchem.7b05046
    11. David A. Hanna, Osiris Martinez-Guzman, and Amit R. Reddi . Heme Gazing: Illuminating Eukaryotic Heme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors. Biochemistry 2017, 56 (13) , 1815-1823. https://doi.org/10.1021/acs.biochem.7b00007
    12. Amit R. Reddi and Iqbal Hamza . Heme Mobilization in Animals: A Metallolipid’s Journey. Accounts of Chemical Research 2016, 49 (6) , 1104-1110. https://doi.org/10.1021/acs.accounts.5b00553
    13. Satu Lahtinen, Qi Wang, and Tero Soukka . Long-Lifetime Luminescent Europium(III) Complex as an Acceptor in an Upconversion Resonance Energy Transfer Based Homogeneous Assay. Analytical Chemistry 2016, 88 (1) , 653-658. https://doi.org/10.1021/acs.analchem.5b02228
    14. T. Hirayama. Construction of Heme and Non-heme Iron Sensor Compounds, Which are Very Useful for Live-cell Imaging. 2025, 249-262. https://doi.org/10.1039/9781837677979-00249
    15. Mina Ahmadi, Zhuangyu Zhao, Ivan J. Dmochowski. RIBOsensor for FRET-based, real-time ribose measurements in live cells. Chemical Science 2025, 16 (18) , 8125-8135. https://doi.org/10.1039/D5SC00244C
    16. Daisuke Tsuji, Tasuku Hirayama, Kanta Kawai, Hideko Nagasawa, Reiko Akagi. Application of fluorescent probe for labile heme quantification in physiological dynamics. Biochimica et Biophysica Acta (BBA) - General Subjects 2024, 1868 (11) , 130707. https://doi.org/10.1016/j.bbagen.2024.130707
    17. Bingxiao Wen, Bernhard Grimm. A genetically encoded fluorescent heme sensor detects free heme in plants. Plant Physiology 2024, 196 (2) , 830-841. https://doi.org/10.1093/plphys/kiae291
    18. Audrey Belot, Herve Puy, Iqbal Hamza, Herbert L. Bonkovsky. Update on heme biosynthesis, tissue‐specific regulation, heme transport, relation to iron metabolism and cellular energy. Liver International 2024, 44 (9) , 2235-2250. https://doi.org/10.1111/liv.15965
    19. Iramofu M. Dominic, Mathilda M. Willoughby, Abigail K. Freer, Courtney M. Moore, Rebecca K. Donegan, Osiris Martinez-Guzman, David A. Hanna, Amit R. Reddi. Fluorometric Methods to Measure Bioavailable and Total Heme. 2024, 151-194. https://doi.org/10.1007/978-1-0716-4043-2_9
    20. Amber L. Grunow, Susan C. Carroll, Alicia N. Kreiman, Molly C. Sutherland, , . Structure-function analysis of the heme-binding WWD domain in the bacterial holocytochrome c synthase, CcmFH. mBio 2023, 14 (6) https://doi.org/10.1128/mbio.01509-23
    21. Brendan J. Mahoney, Andrew K. Goring, Yueying Wang, Poojita Dasika, Anqi Zhou, Emmitt Grossbard, Duilio Cascio, Joseph A. Loo, Robert T. Clubb. Development and atomic structure of a new fluorescence-based sensor to probe heme transfer in bacterial pathogens. Journal of Inorganic Biochemistry 2023, 249 , 112368. https://doi.org/10.1016/j.jinorgbio.2023.112368
    22. Hyojung Kim, Courtney M Moore, Santi Mestre-Fos, David A Hanna, Loren Dean Williams, Amit R Reddi, Matthew P Torres. Depletion assisted hemin affinity (DAsHA) proteomics reveals an expanded landscape of heme-binding proteins in the human proteome. Metallomics 2023, 15 (3) https://doi.org/10.1093/mtomcs/mfad004
    23. Peng Xue, Eddy Sánchez-León, Djihane Damoo, Guanggan Hu, Won Hee Jung, James W. Kronstad. Heme sensing and trafficking in fungi. Fungal Biology Reviews 2023, 43 , 100286. https://doi.org/10.1016/j.fbr.2022.09.002
    24. Aileen Krüger, Marc Keppel, Vikas Sharma, Julia Frunzke. The diversity of heme sensor systems – heme-responsive transcriptional regulation mediated by transient heme protein interactions. FEMS Microbiology Reviews 2022, 46 (3) https://doi.org/10.1093/femsre/fuac002
    25. Vasiliki‐Dimitra C. Tsolaki, Sofia K. Georgiou‐Siafis, Athina I. Tsamadou, Stefanos A. Tsiftsoglou, Martina Samiotaki, George Panayotou, Asterios S. Tsiftsoglou. Hemin accumulation and identification of a heme‐binding protein clan in K562 cells by proteomic and computational analysis. Journal of Cellular Physiology 2022, 237 (2) , 1315-1340. https://doi.org/10.1002/jcp.30595
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    29. Galvin C.-H. Leung, Simon S.-P. Fung, Andrea E. Gallio, Robert Blore, Dominic Alibhai, Emma L. Raven, Andrew J. Hudson. Unravelling the mechanisms controlling heme supply and demand. Proceedings of the National Academy of Sciences 2021, 118 (22) https://doi.org/10.1073/pnas.2104008118
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    31. Yuanqiang Sun, Pengjuan Sun, Wei Guo. Fluorescent probes for iron, heme, and related enzymes. Coordination Chemistry Reviews 2021, 429 , 213645. https://doi.org/10.1016/j.ccr.2020.213645
    32. Ian G. Chambers, Mathilda M. Willoughby, Iqbal Hamza, Amit R. Reddi. One ring to bring them all and in the darkness bind them: The trafficking of heme without deliverers. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2021, 1868 (1) , 118881. https://doi.org/10.1016/j.bbamcr.2020.118881
    33. Joachim Kloehn, Clare R. Harding, Dominique Soldati‐Favre. Supply and demand—heme synthesis, salvage and utilization by Apicomplexa. The FEBS Journal 2021, 288 (2) , 382-404. https://doi.org/10.1111/febs.15445
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    35. Liu Liu, Arti B. Dumbrepatil, Angela S. Fleischhacker, E. Neil G. Marsh, Stephen W. Ragsdale. Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site. Journal of Biological Chemistry 2020, 295 (50) , 17227-17240. https://doi.org/10.1074/jbc.RA120.014919
    36. Santi Mestre-Fos, Chieri Ito, Courtney M. Moore, Amit R. Reddi, Loren Dean Williams. Human ribosomal G-quadruplexes regulate heme bioavailability. Journal of Biological Chemistry 2020, 295 (44) , 14855-14865. https://doi.org/10.1074/jbc.RA120.014332
    37. Gaurav Bairwa, Eddy Sánchez-León, Eunsoo Do, Won Hee Jung, James W. Kronstad, . A Cytoplasmic Heme Sensor Illuminates the Impacts of Mitochondrial and Vacuolar Functions and Oxidative Stress on Heme-Iron Homeostasis in Cryptococcus neoformans. mBio 2020, 11 (4) https://doi.org/10.1128/mBio.00986-20
    38. Amy Bergmann, Katherine Floyd, Melanie Key, Carly Dameron, Kerrick C. Rees, L. Brock Thornton, Daniel C. Whitehead, Iqbal Hamza, Zhicheng Dou, . Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection. PLOS Pathogens 2020, 16 (5) , e1008499. https://doi.org/10.1371/journal.ppat.1008499
    39. Samantha A. Swenson, Courtney M. Moore, Jason R. Marcero, Amy E. Medlock, Amit R. Reddi, Oleh Khalimonchuk. From Synthesis to Utilization: The Ins and Outs of Mitochondrial Heme. Cells 2020, 9 (3) , 579. https://doi.org/10.3390/cells9030579
    40. Neha Soleja, Mohd. Mohsin. Opportunities for Real-Time Monitoring of Biomolecules Using FRET-Based Nanosensors. 2020, 1-14. https://doi.org/10.1007/978-981-15-8346-9_1
    41. Amreen, Mohammad Ahmad, Ruphi Naz. Recent Advances of Fluorescence Resonance Energy Transfer-Based Nanosensors for the Detection of Human Ailments. 2020, 157-173. https://doi.org/10.1007/978-981-15-8346-9_8
    42. Meghan M. Verstraete, L. Daniela Morales, Marek J. Kobylarz, Slade A. Loutet, Holly A. Laakso, Tyler B. Pinter, Martin J. Stillman, David E. Heinrichs, Michael E.P. Murphy. The heme-sensitive regulator SbnI has a bifunctional role in staphyloferrin B production by Staphylococcus aureus. Journal of Biological Chemistry 2019, 294 (30) , 11622-11636. https://doi.org/10.1074/jbc.RA119.007757
    43. Ovais Manzoor, Neha Soleja, Parvez Khan, Md. Imtaiyaz Hassan, Mohd Mohsin. Visualization of thiamine in living cells using genetically encoded fluorescent nanosensor. Biochemical Engineering Journal 2019, 146 , 170-178. https://doi.org/10.1016/j.bej.2019.03.018
    44. Galvin C.-H. Leung, Simon S.-P. Fung, Nicholas R.B. Dovey, Emma L. Raven, Andrew J. Hudson. Precise determination of heme binding affinity in proteins. Analytical Biochemistry 2019, 572 , 45-51. https://doi.org/10.1016/j.ab.2019.02.021
    45. Rebecca K. Donegan, Courtney M. Moore, David A. Hanna, Amit R. Reddi. Handling heme: The mechanisms underlying the movement of heme within and between cells. Free Radical Biology and Medicine 2019, 133 , 88-100. https://doi.org/10.1016/j.freeradbiomed.2018.08.005
    46. Jagpreet Singh Sidhu, Ashutosh Singh, Neha Garg, Navneet Kaur, Narinder Singh. Gold conjugated carbon dots nano assembly: FRET paired fluorescence probe for cysteine recognition. Sensors and Actuators B: Chemical 2019, 282 , 515-522. https://doi.org/10.1016/j.snb.2018.11.105
    47. Laura D. Newton, Sofia I. Pascu, Rex M. Tyrrell, Ian M. Eggleston. Development of a peptide-based fluorescent probe for biological heme monitoring. Organic & Biomolecular Chemistry 2019, 17 (3) , 467-471. https://doi.org/10.1039/C8OB02290A
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    49. Biswash Thakuri, Amanda B. Graves, Alex Chao, Sommer L. Johansen, Celia W. Goulding, Matthew D. Liptak. The affinity of MhuD for heme is consistent with a heme degrading function in vivo. Metallomics 2018, 10 (11) , 1560-1563. https://doi.org/10.1039/C8MT00238J
    50. David A. Hanna, Rebecca Hu, Hyojung Kim, Osiris Martinez-Guzman, Matthew P. Torres, Amit R. Reddi. Heme bioavailability and signaling in response to stress in yeast cells. Journal of Biological Chemistry 2018, 293 (32) , 12378-12393. https://doi.org/10.1074/jbc.RA118.002125
    51. Sitara B. Sankar, Rebecca K. Donegan, Kajol J. Shah, Amit R. Reddi, Levi B. Wood. Heme and hemoglobin suppress amyloid β–mediated inflammatory activation of mouse astrocytes. Journal of Biological Chemistry 2018, 293 (29) , 11358-11373. https://doi.org/10.1074/jbc.RA117.001050
    52. Jonathan M. Comer, Li Zhang. Experimental Methods for Studying Cellular Heme Signaling. Cells 2018, 7 (6) , 47. https://doi.org/10.3390/cells7060047
    53. Ziyang Hao, Rongfeng Zhu, Peng R Chen. Genetically encoded fluorescent sensors for measuring transition and heavy metals in biological systems. Current Opinion in Chemical Biology 2018, 43 , 87-96. https://doi.org/10.1016/j.cbpa.2017.12.002
    54. Yosuke Hisamatsu, Naoki Umezawa, Hirokazu Yagi, Koichi Kato, Tsunehiko Higuchi. Design and synthesis of a 4-aminoquinoline-based molecular tweezer that recognizes protoporphyrin IX and iron( iii ) protoporphyrin IX and its application as a supramolecular photosensitizer. Chemical Science 2018, 9 (38) , 7455-7467. https://doi.org/10.1039/C8SC02133C
    55. Amelie Wißbrock, Diana Imhof. A Tough Nut to Crack: Intracellular Detection and Quantification of Heme in Malaria Parasites by a Genetically Encoded Protein Sensor. ChemBioChem 2017, 18 (16) , 1561-1564. https://doi.org/10.1002/cbic.201700274
    56. James R. Abshire, Christopher J. Rowlands, Suresh M. Ganesan, Peter T. C. So, Jacquin C. Niles. Quantification of labile heme in live malaria parasites using a genetically encoded biosensor. Proceedings of the National Academy of Sciences 2017, 114 (11) https://doi.org/10.1073/pnas.1615195114
    57. Lynn Sanford, Amy Palmer. Recent Advances in Development of Genetically Encoded Fluorescent Sensors. 2017, 1-49. https://doi.org/10.1016/bs.mie.2017.01.019
    58. Matthew A. Conger, Deepika Pokhrel, Matthew D. Liptak. Tight binding of heme to Staphylococcus aureus IsdG and IsdI precludes design of a competitive inhibitor. Metallomics 2017, 9 (5) , 556-563. https://doi.org/10.1039/C7MT00035A
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    61. Margaret C. Carpenter, Amy E. Palmer. Unraveling the mystery of the ring: Tracking heme dynamics in living cells. Proceedings of the National Academy of Sciences 2016, 113 (27) , 7296-7297. https://doi.org/10.1073/pnas.1607505113
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    Cite this: ACS Chem. Biol. 2015, 10, 7, 1610–1615
    Click to copy citationCitation copied!
    https://doi.org/10.1021/cb5009734
    Published April 10, 2015
    Copyright © 2015 American Chemical Society
    Request reuse permissions

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