Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension
Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca<sup>2+</sup> signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules l...
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MDPI AG
2022-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/3/473 |
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| author | Jorge Reyes-García Abril Carbajal-García Annarita Di Mise Yun-Min Zheng Xiangdong Wang Yong-Xiao Wang |
| author_facet | Jorge Reyes-García Abril Carbajal-García Annarita Di Mise Yun-Min Zheng Xiangdong Wang Yong-Xiao Wang |
| author_sort | Jorge Reyes-García |
| collection | DOAJ |
| description | Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca<sup>2+</sup> signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron–sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca<sup>2+</sup> levels. Mitochondrial ROS and Ca<sup>2+</sup> can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. Evidence suggests that increased mitochondrial ROS and Ca<sup>2+</sup> signaling leads to abnormal synthesis of ketones, which play a critical role in the development of PH. In this review, we discuss some of the recent findings on the important interactive role and molecular mechanisms of mitochondrial ROS and Ca<sup>2+</sup> in the development and progression of PH. We also address the contributions of NF-κB-dependent inflammatory responses and ketone-mediated oxidative stress due to abnormal regulation of mitochondrial ROS and Ca<sup>2+</sup> signaling in PH. |
| first_indexed | 2024-03-09T13:53:23Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:53:23Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c354440de7a345e89f9025bca5cee3bd2023-11-30T20:47:43ZengMDPI AGAntioxidants2076-39212022-02-0111347310.3390/antiox11030473Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary HypertensionJorge Reyes-García0Abril Carbajal-García1Annarita Di Mise2Yun-Min Zheng3Xiangdong Wang4Yong-Xiao Wang5Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY 12208, USADepartment of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Ciudad de Mexico 04519, MexicoDepartment of Molecular & Cellular Physiology, Albany Medical College, Albany, NY 12208, USADepartment of Molecular & Cellular Physiology, Albany Medical College, Albany, NY 12208, USADepartment of Pulmonary and Critical Care Medicine, Shanghai Engineering Research for AI Technology for Cardiopulmonary, Shanghai 200032, ChinaDepartment of Molecular & Cellular Physiology, Albany Medical College, Albany, NY 12208, USAMitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca<sup>2+</sup> signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron–sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca<sup>2+</sup> levels. Mitochondrial ROS and Ca<sup>2+</sup> can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. Evidence suggests that increased mitochondrial ROS and Ca<sup>2+</sup> signaling leads to abnormal synthesis of ketones, which play a critical role in the development of PH. In this review, we discuss some of the recent findings on the important interactive role and molecular mechanisms of mitochondrial ROS and Ca<sup>2+</sup> in the development and progression of PH. We also address the contributions of NF-κB-dependent inflammatory responses and ketone-mediated oxidative stress due to abnormal regulation of mitochondrial ROS and Ca<sup>2+</sup> signaling in PH.https://www.mdpi.com/2076-3921/11/3/473pulmonary hypertensionmitochondrial ROSketonesCa<sup>2+</sup> signaling |
| spellingShingle | Jorge Reyes-García Abril Carbajal-García Annarita Di Mise Yun-Min Zheng Xiangdong Wang Yong-Xiao Wang Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension Antioxidants pulmonary hypertension mitochondrial ROS ketones Ca<sup>2+</sup> signaling |
| title | Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension |
| title_full | Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension |
| title_fullStr | Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension |
| title_full_unstemmed | Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension |
| title_short | Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension |
| title_sort | important functions and molecular mechanisms of mitochondrial redox signaling in pulmonary hypertension |
| topic | pulmonary hypertension mitochondrial ROS ketones Ca<sup>2+</sup> signaling |
| url | https://www.mdpi.com/2076-3921/11/3/473 |
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