An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption.
An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption.
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DOI：
10.1038/s41586-023-06611-6
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发表时间：
2023-10
期刊：
影响因子：
64.8
通讯作者：
Sun, Qiang
中科院分区：
文献类型：
--
作者：
Zhang, Feng;Zhang, Bo;Wang, Yuying;Jiang, Runmin;Liu, Jin;Wei, Yuexian;Gao, Xinyue;Zhu, Yichao;Wang, Xinli;Sun, Mao;Kang, Junjun;Liu, Yingying;You, Guoxing;Wei, Ding;Xin, Jiajia;Bao, Junxiang;Wang, Meiqing;Gu, Yu;Wang, Zhe;Ye, Jing;Guo, Shuangping;Huang, Hongyan;Sun, Qiang
虽然血红蛋白是红细胞中已知的氧载体，其功能是长距离运输氧，但其在红细胞外的生理作用在很大程度上是难以捉摸的。在这里，我们发现软骨细胞产生大量的血红蛋白，在细胞质中形成嗜酸性粒细胞阳性小体。血红蛋白体（Hedy）是一种无膜凝聚物，其特征是相分离。软骨细胞中血红蛋白的产生受缺氧控制，并且依赖于KLF 1而不是HIF 1/2α途径。软骨细胞中血红蛋白的缺失导致Hedy损失沿着严重缺氧、糖酵解增强和软骨组织中心的广泛细胞死亡，这归因于缺氧条件下Hedy控制的氧供应的损失。这些结果证明了血红蛋白在软骨细胞中的红细胞外作用，并揭示了软骨细胞通过Hedy在缺氧环境中存活的迄今未被认识的机制。软骨细胞产生的血红蛋白在其细胞质中形成嗜酸性粒细胞阳性血红蛋白小体，这些小体的缺失会导致严重的缺氧。
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 elusive. 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. Haemoglobin produced by chondrocytes forms eosin-positive haemoglobin bodies in their cytoplasm, and deletion of these bodies causes severe hypoxia.
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DOI：
10.1073/pnas.92.20.9259
发表时间：
1995-09-26
影响因子：
11.1
作者：
CIAVATTA, DJ;RYAN, TM;TOWNES, TM
通讯作者：
TOWNES, TM
DOI：
10.1073/pnas.0813216106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
64.8
作者：
Garry, DJ;Ordway, GA;Williams, RS
通讯作者：
Williams, RS
影响因子：
64.8
作者：
NUEZ, B;MICHALOVICH, D;GROSVELD, F
通讯作者：
GROSVELD, F
影响因子：
7.2
作者：
Long, Fanxin;Ornitz, David M.
通讯作者：
Ornitz, David M.