التفاصيل البيبلوغرافية
| العنوان: |
Upregulation of mitochondrial ATPase inhibitory factor 1 (ATPIF1) mediates increased glycolysis in mouse hearts |
| المؤلفون: |
Bo Zhou, Arianne Caudal, Xiaoting Tang, Juan D. Chavez, Timothy S. McMillen, Andrew Keller, Outi Villet, Mingyue Zhao, Yaxin Liu, Julia Ritterhoff, Pei Wang, Stephen C. Kolwicz Jr., Wang Wang, James E. Bruce, Rong Tian |
| المصدر: |
The Journal of Clinical Investigation, Vol 132, Iss 10 (2022) |
| بيانات النشر: |
American Society for Clinical Investigation |
| سنة النشر: |
2022 |
| المجموعة: |
Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: |
Cardiology, Metabolism, Medicine |
| الوصف: |
In hypertrophied and failing hearts, fuel metabolism is reprogrammed to increase glucose metabolism, especially glycolysis. This metabolic shift favors biosynthetic function at the expense of ATP production. Mechanisms responsible for the switch are poorly understood. We found that inhibitory factor 1 of the mitochondrial FoF1-ATP synthase (ATPIF1), a protein known to inhibit ATP hydrolysis by the reverse function of ATP synthase during ischemia, was significantly upregulated in pathological cardiac hypertrophy induced by pressure overload, myocardial infarction, or α-adrenergic stimulation. Chemical cross-linking mass spectrometry analysis of hearts hypertrophied by pressure overload suggested that increased expression of ATPIF1 promoted the formation of FoF1-ATP synthase nonproductive tetramer. Using ATPIF1 gain- and loss-of-function cell models, we demonstrated that stalled electron flow due to impaired ATP synthase activity triggered mitochondrial ROS generation, which stabilized HIF1α, leading to transcriptional activation of glycolysis. Cardiac-specific deletion of ATPIF1 in mice prevented the metabolic switch and protected against the pathological remodeling during chronic stress. These results uncover a function of ATPIF1 in nonischemic hearts, which gives FoF1-ATP synthase a critical role in metabolic rewiring during the pathological remodeling of the heart. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
1558-8238 |
| Relation: |
https://doi.org/10.1172/JCI155333; https://doaj.org/toc/1558-8238; https://doaj.org/article/42430db1c8a448f4bb8c08df2e4cb07e |
| الاتاحة: |
https://doaj.org/article/42430db1c8a448f4bb8c08df2e4cb07e |
| رقم الانضمام: |
edsbas.936BF543 |
| قاعدة البيانات: |
BASE |
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