An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption

Feng Zhang (), Bo Zhang, Yuying Wang, Runmin Jiang, Jin Liu, Yuexian Wei, Xinyue Gao, Yichao Zhu, Xinli Wang, Mao Sun, Junjun Kang, Yingying Liu, Guoxing You, Ding Wei, Jiajia Xin, Junxiang Bao, Meiqing Wang, Yu Gu, Zhe Wang, Jing Ye, Shuangping Guo, Hongyan Huang and Qiang Sun ()
Additional contact information
Feng Zhang: The Fourth Military Medical University
Bo Zhang: Chinese Academy of Medical Science
Yuying Wang: The Fourth Military Medical University
Runmin Jiang: The Fourth Military Medical University
Jin Liu: The Fourth Military Medical University
Yuexian Wei: Chinese Academy of Medical Science
Xinyue Gao: Chinese Academy of Medical Science
Yichao Zhu: Chinese Academy of Medical Science
Xinli Wang: The Fourth Military Medical University
Mao Sun: The Fourth Military Medical University
Junjun Kang: The Fourth Military Medical University
Yingying Liu: The Fourth Military Medical University
Guoxing You: Academy of Military Medical Sciences
Ding Wei: The Fourth Military Medical University
Jiajia Xin: The Fourth Military Medical University
Junxiang Bao: The Fourth Military Medical University
Meiqing Wang: The Fourth Military Medical University
Yu Gu: The Fourth Military Medical University
Zhe Wang: The Fourth Military Medical University
Jing Ye: The Fourth Military Medical University
Shuangping Guo: The Fourth Military Medical University
Hongyan Huang: Beijing Shijitan Hospital of Capital Medical University
Qiang Sun: Chinese Academy of Medical Science

Nature, 2023, vol. 622, issue 7984, 834-841

Abstract: Abstract Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive1,2. Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.

Date: 2023
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DOI: 10.1038/s41586-023-06611-6

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