Mitochondrial flashes regulate ATP homeostasis in the heart
The maintenance of a constant ATP level (‘set-point’) is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/23908 |
| _version_ | 1811253220431888384 |
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| author | Xianhua Wang Xing Zhang Di Wu Zhanglong Huang Tingting Hou Chongshu Jian Peng Yu Fujian Lu Rufeng Zhang Tao Sun Jinghang Li Wenfeng Qi Yanru Wang Feng Gao Heping Cheng |
| author_facet | Xianhua Wang Xing Zhang Di Wu Zhanglong Huang Tingting Hou Chongshu Jian Peng Yu Fujian Lu Rufeng Zhang Tao Sun Jinghang Li Wenfeng Qi Yanru Wang Feng Gao Heping Cheng |
| author_sort | Xianhua Wang |
| collection | DOAJ |
| description | The maintenance of a constant ATP level (‘set-point’) is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of ATP homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes), recently discovered dynamic activity of mitochondria, play an essential role for the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes negatively regulate ATP production in isolated respiring mitochondria and, their activity waxes and wanes to counteract the ATP supply-demand imbalance caused by superfluous substrate and altered workload in cardiomyocytes. Moreover, manipulating mitoflash activity is sufficient to inversely shift the otherwise stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage through F1Fo-ATP synthase appears to mediate the coupling between mitoflash production and ATP set-point regulation. These findings indicate mitoflashes appear to constitute a digital auto-regulator for ATP homeostasis in the heart. |
| first_indexed | 2024-04-12T16:46:38Z |
| format | Article |
| id | doaj.art-f2152f0a05554df6ad1ed29ca805eb9c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:46:38Z |
| publishDate | 2017-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f2152f0a05554df6ad1ed29ca805eb9c2022-12-22T03:24:33ZengeLife Sciences Publications LtdeLife2050-084X2017-07-01610.7554/eLife.23908Mitochondrial flashes regulate ATP homeostasis in the heartXianhua Wang0https://orcid.org/0000-0002-2016-9415Xing Zhang1Di Wu2Zhanglong Huang3Tingting Hou4Chongshu Jian5Peng Yu6Fujian Lu7Rufeng Zhang8Tao Sun9Jinghang Li10Wenfeng Qi11Yanru Wang12Feng Gao13Heping Cheng14State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaDepartment of Aerospace Medicine, The Fourth Military Medical University, Xi'an, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaDepartment of Aerospace Medicine, The Fourth Military Medical University, Xi'an, ChinaState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaThe maintenance of a constant ATP level (‘set-point’) is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of ATP homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes), recently discovered dynamic activity of mitochondria, play an essential role for the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes negatively regulate ATP production in isolated respiring mitochondria and, their activity waxes and wanes to counteract the ATP supply-demand imbalance caused by superfluous substrate and altered workload in cardiomyocytes. Moreover, manipulating mitoflash activity is sufficient to inversely shift the otherwise stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage through F1Fo-ATP synthase appears to mediate the coupling between mitoflash production and ATP set-point regulation. These findings indicate mitoflashes appear to constitute a digital auto-regulator for ATP homeostasis in the heart.https://elifesciences.org/articles/23908mitochondriamitochondrial flashesATP homeostasisenergy metabolismheart |
| spellingShingle | Xianhua Wang Xing Zhang Di Wu Zhanglong Huang Tingting Hou Chongshu Jian Peng Yu Fujian Lu Rufeng Zhang Tao Sun Jinghang Li Wenfeng Qi Yanru Wang Feng Gao Heping Cheng Mitochondrial flashes regulate ATP homeostasis in the heart eLife mitochondria mitochondrial flashes ATP homeostasis energy metabolism heart |
| title | Mitochondrial flashes regulate ATP homeostasis in the heart |
| title_full | Mitochondrial flashes regulate ATP homeostasis in the heart |
| title_fullStr | Mitochondrial flashes regulate ATP homeostasis in the heart |
| title_full_unstemmed | Mitochondrial flashes regulate ATP homeostasis in the heart |
| title_short | Mitochondrial flashes regulate ATP homeostasis in the heart |
| title_sort | mitochondrial flashes regulate atp homeostasis in the heart |
| topic | mitochondria mitochondrial flashes ATP homeostasis energy metabolism heart |
| url | https://elifesciences.org/articles/23908 |
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