Elevated ROS depress mitochondrial oxygen utilization efficiency in cardiomyocytes during acute hypoxia
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OLECULAR AND CELLULAR MECHANISMS OF DISEASE
Elevated ROS depress mitochondrial oxygen utilization efficiency in cardiomyocytes during acute hypoxia Ru-Zhou Zhao 1 & Xiao-Bo Wang 1 & Shuai Jiang 1 & Ning-Yu Ru 1 & Bo Jiao 1 & Yun-Ying Wang 1 & Zhi-Bin Yu 1 Received: 13 March 2020 / Revised: 24 July 2020 / Accepted: 7 September 2020 / Published online: 17 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Mitochondria are important sites for the production of ATP and the generation of ROS in cells. However, whether acute hypoxia increases ROS generation in cells or affects ATP production remains unclear, and therefore, monitoring the changes in ATP and ROS in living cells in real time is important. In this study, cardiomyocytes were transfected with RoGFP for ROS detection and MitGO-Ateam2 for ATP detection, whereby ROS and ATP production in cardiomyocytes were respectively monitored in real time. Furthermore, the oxygen consumption rate (OCR) of cardiomyocytes was measured. Similar results were produced for adult and neonatal rat cardiomyocytes. Hypoxia (1% O2) reduced the basal OCR, ATP-linked OCR, and maximal OCR in cardiomyocytes compared with these OCR levels in the cardiomyocytes in the normoxic group (21% O2). However, ATP-linked OCR, normalized to maximal OCR, was increased during hypoxia, indicating that the electron leakage of complex III exacerbated the increase of ATP-linked oxygen consumption during hypoxia and vice versa. Combined with the result that cardiomyocytes expressing MitGO-Ateam2 showed a significant decrease in ATP production during hypoxia compared with that of normoxic group, acute hypoxia might depress the mitochondrial oxygen utilization efficiency of the cardiomyocytes. Moreover, cardiomyocytes expressing Cyto-RoGFP or IMS-RoGFP showed an increase in ROS generation in the cytosol and the mitochondrial intermembrane space (IMS) during hypoxia. All of these results indicate that acute hypoxia generated more ROS in complex III and increased mitochondrial oxygen consumption, leading to less ATP production. In conclusion, acute hypoxia depresses the mitochondrial oxygen utilization efficiency by decreasing ATP production and increasing oxygen consumption as a result of the enhanced ROS generation at mitochondrial complex III. Keywords Hypoxia . Cardiomyocyte . ATP production . ROS generation . Mitochondrial oxygen consumption . Oxygen utilization efficiency
Ru-Zhou Zhao and Xiao-Bo Wang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00424-020-02463-5) contains supplementary material, which is available to authorized users. * Yun-Ying Wang [email protected]
Shuai Jiang [email protected]
* Zhi-Bin Yu [email protected]
Ning-Yu Ru [email protected]
Ru-Zhou Zhao [email protected] Xiao-Bo Wang [email protected]
Bo Jiao [email protected] 1
Department of Aerospace Physiology, Fourth Military Medical University, 169# Changle West Road, Xi’an 710032, China
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