Cited by 312Mitochondrial Function and PathologyAutophagy in Disease and TherapyCardiovascular Function and Risk Factors

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Hyperglycemia-Driven Inhibition of AMP-Activated Protein Kinase α2 Induces Diabetic Cardiomyopathy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes In Vivo

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Wu, Shengnan, Lu, Qiulun, Ding, Ye, Wu, Yin, Qiu, Yu, Wang, Pei, Mao, Xiaoxiang, Huang, Kai, Xie, Zhonglin, Zou, Ming-Hui·2019·Circulation

DOI 10.1161/circulationaha.118.033552PMC PMC6465113

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Abstract

Background: Fundc1 (FUN14 domain containing 1), an outer mitochondrial membrane protein, is important for mitophagy and mitochondria-associated endoplasmic reticulum membranes (MAMs). The roles of Fundc1 and MAMs in diabetic hearts remain unknown. The aims of this study, therefore, were to determine whether the diabetes mellitus–induced Fundc1 expression could increase MAM formation, and whether disruption of MAM formation improves diabetic cardiac function. Methods: Levels of FUNDC1 were examined in the hearts from diabetic patients and nondiabetic donors. Levels of Fundc1-induced MAMs and mitochondrial and heart function were examined in mouse neonatal cardiomyocytes exposed to high glucose (HG, 30 mmol/L d -glucose for 48 hours), and in streptozotocin-treated cardiac-specific Fundc1 knockout mice and cardiac-specific Fundc1 knockout diabetic Akita mice, as well. Results: FUNDC1 levels were significantly elevated in cardiac tissues from diabetic patients in comparison with those from nondiabetic donors. In cultured mouse neonatal cardiomyocytes, HG conditions increased levels of Fundc1, the inositol 1,4,5-trisphosphate type 2 receptor (Ip 3 r2), and MAMs. Genetic downregulation of either Fundc1 or Ip 3 r2 inhibited MAM formation, reduced endoplasmic reticulum-mitochondrial Ca 2+ flux, and improved mitochondrial function in HG-treated cardiomyocytes. Consistently, adenoviral overexpression of Fundc1 promoted MAM formation, mitochondrial Ca 2+ increase, and mitochondrial dysfunction in cardiomyocytes exposed to normal glucose (5.5 mmol/L d -glucose). In comparison with nondiabetic controls, levels of Fundc1, Ip 3 r2, and MAMs were significantly increased in hearts from streptozotocin-treated mice and Akita mice. Furthermore, in comparison with control hearts, diabetes mellitus markedly increased coimmunoprecipitation of Fundc1 and Ip 3 r2. The binding of Fundc1 to Ip 3 r2 inhibits Ip 3 r2 ubiquitination and proteasome-mediated degradation. Cardiomyocyte-specific Fundc1 deletion ablated diabetes mellitus–induced MAM formation, prevented mitochondrial Ca 2+ increase, mitochondrial fragmentation, and apoptosis with improved mitochondrial functional capacity and cardiac function. In mouse neonatal cardiomyocytes, HG suppressed AMP-activated protein kinase activity. Furthermore, in cardiomyocytes of Prkaa2 knockout mice, expression of Fundc1, MAM formation, and mitochondrial Ca 2+ levels were significantly increased. Finally, adenoviral overexpression of a constitutively active mutant AMP-activated protein kinase ablated HG-induced MAM formation and mitochondrial dysfunction. Conclusions: We conclude that diabetes mellitus suppresses AMP-activated protein kinase, initiating Fundc1-mediated MAM formation, mitochondrial dysfunction, and cardiomyopathy, suggesting that AMP-activated protein kinase–induced Fundc1 suppression is a valid target to treat diabetic cardiomyopathy.

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Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Down-Regulation of Na+/K+ATPase Activity by Human Parvovirus B19 Capsid Protein VP1
Almilaji, A., Szteyn, K., Fein, E., Pakladok, T., Muñoz, C., Elvira, B., Towhid, S. T., Alesutan, I., Shumilina, E. V., Bock, C. –., et al. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350083 · Cited by 8,700
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
(1998) · The Lancet · doi:10.1016/s0140-6736(98)07037-8 · Cited by 8,247
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy
Cillà, S. D., Farruggio, S., Vujosevic, S., Raina, G., Filippini, D. A., Gatti, V., Clemente, N., Mary, D., Vezzola, D., Casini, G., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479441 · Cited by 5,154
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.
(1998) · PubMed · Cited by 4,290
The Pathophysiology of Mitochondrial Cell Death
Green, D. R., & Kroemer, G. (2004) · Science · doi:10.1126/science.1099320 · Cited by 3,487
Regulation of cell death: the calcium–apoptosis link
Orrenius, S., Zhivotovsky, B., & Nicotera, P. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1150 · Cited by 3,060
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321

Flagged first, then by citations

Show all 78 references

Sorted by citations

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Ren, J., Bi, Y., Sowers, J. R., Hetz, C., & Zhang, Y. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00511-w · Cited by 708
Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis
Packer, M. (2022) · Circulation · doi:10.1161/circulationaha.122.061732 · Cited by 456
Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications
Ren, J. T., Wu, N. N., Wang, S., Sowers, J. R., & Zhang, Y. (2021) · Physiological Reviews · doi:10.1152/physrev.00030.2020 · Cited by 388
Regulation of Mitochondrial ATP Production: Ca2+ Signaling and Quality Control
Boyman, L., Karbowski, M., & Lederer, W. J. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.10.007 · Cited by 310
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286
Mitochondrial ROS Formation in the Pathogenesis of Diabetic Cardiomyopathy
Kaludercic, N., & Lisa, F. D. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00012 · Cited by 268
Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia‐reperfusion injury by improving mitochondrial quality control: Role of SIRT6
Yu, L., Dong, X., Xue, X., Xu, S. C., Zhang, X., Xu, Y., Wang, Z., Wang, Y., Gao, H., Liang, Y., et al. (2020) · Journal of Pineal Research · doi:10.1111/jpi.12698 · Cited by 222
FUNDC1-dependent mitophagy induced by tPA protects neurons against cerebral ischemia-reperfusion injury
Cai, Y., Yang, E., Yao, X., Zhang, X., Wang, Q., Wang, Y., Liu, J., Fan, W., Yi, K., Kang, C., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101792 · Cited by 198
Potential role of mitochondria-associated endoplasmic reticulum membrane proteins in diseases
Mao, H. Z., Chen, W., Chen, L., & Li, L. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115011 · Cited by 164
FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis
Pei, Z., Liu, Y., Liu, S., Wei, J. J., Luo, Y., Sun, M., Duan, Y., Ajoolabady, A., Sowers, J. R., Fang, Y., et al. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154840 · Cited by 152
Reduced reticulum–mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy
Dia, M., Gomez, L., Thibault, H., Tessier, N., Léon, C., Chouabe, C., Ducreux, S., Gallo-Bona, N., Tubbs, E., Bendridi, N., et al. (2020) · Basic Research in Cardiology · doi:10.1007/s00395-020-00835-7 · Cited by 160
Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction
Schiattarella, G. G., Altamirano, F. J., Kim, S. Y., Tong, D., Ferdous, A., Piristine, H. C., Dasgupta, S., Wang, X., French, K. M., Villalobos, E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21931-9 · Cited by 145
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Xie, S., Liu, S., Zhang, T., Shi, W., Xing, Y., Fang, W., Zhang, M., Chen, M.-Y., Xu, S., Fan, M.-Q., et al. (2023) · Circulation · doi:10.1161/circulationaha.123.065603 · Cited by 147
Mitochondrial quality surveillance as a therapeutic target in myocardial infarction
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FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes are involved in angiogenesis and neoangiogenesis
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Mitochondria-Associated Endoplasmic Reticulum Membranes in Cardiovascular Diseases
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Molecular Mechanisms and Regulation of Mammalian Mitophagy
Choubey, V., Zeb, A., & Kaasik, A. (2021) · Cells · doi:10.3390/cells11010038 · Cited by 128
The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and Ca2+ transport in the pathogenesis of diseases
Zhao, W., & Sheng, R. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01359-9 · Cited by 128
Akap1 deficiency exacerbates diabetic cardiomyopathy in mice by NDUFS1-mediated mitochondrial dysfunction and apoptosis
Qi, B., He, L., Zhao, Y., Zhang, L., He, Y., Li, J., Li, C., Zhang, B., Huang, Q., Xing, J., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05103-w · Cited by 116
Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKIIδ pathway in vitro and in vivo
Song, Z., Song, H., Liu, D., Yan, B., Wang, D., Zhang, Y., Zhao, X., Tian, X., Yan, C., & Han, Y. (2022) · Theranostics · doi:10.7150/thno.65716 · Cited by 115
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Markovinović, A., Greig, J., Martín‐Guerrero, S. M., Salam, S., & Paillusson, S. (2022) · Journal of Cell Science · doi:10.1242/jcs.248534 · Cited by 123
Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms
Huang, K., Luo, X., Liao, B., Li, G., & Feng, J. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01816-5 · Cited by 117
Activation of TRPV1 channel antagonizes diabetic nephropathy through inhibiting endoplasmic reticulum-mitochondria contact in podocytes
Wei, X., Wei, X., Lu, Z., Li, L., Hu, Y., Sun, F., Jiang, Y., Ma, H., Zheng, H., Yang, G., et al. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154182 · Cited by 110
PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming
Ma, W., Sun, X., Zhu, Y., & Liu, N. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03162-w · Cited by 112
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Lu, J. G., Chen, P. P., Zhang, J. X., Li, X. Q., Wang, G. H., Yuan, B. Y., Huang, S. J., Liu, X. Q., Jiang, T., Wang, M. Y., et al. (2021) · Theranostics · doi:10.7150/thno.56598 · Cited by 96
The Molecular Mechanisms Underlying Mitochondria-Associated Endoplasmic Reticulum Membrane-Induced Insulin Resistance
Cheng, H., Gang, X., He, G., Liu, Y., Wang, Y., Zhao, X. Y., & Wang, G. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.592129 · Cited by 89
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Li, G., Li, J., Shao, R., Zhao, J., & Chen, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.788634 · Cited by 88
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Yang, H., Jiang, H., Tao, J., Zhang, C., Xiong, J., Yang, J., Liu, Y., Zhong, W., Guan, X., Duan, J., et al. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00889-8 · Cited by 88
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Cell death regulation by MAMs: from molecular mechanisms to therapeutic implications in cardiovascular diseases
Li, Y. E., Sowers, J. R., Hetz, C. A., & Ren, J. T. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04942-2 · Cited by 90
The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases
Zhang, W. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.08.011 · Cited by 83
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Liu, H., Zang, C., Yuan, F., Ju, C., Shang, M., Ning, J., Yang, Y., Ma, J., Li, G. L., Bao, X., et al. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114891 · Cited by 87
Bmal1 downregulation leads to diabetic cardiomyopathy by promoting Bcl2/IP3R-mediated mitochondrial Ca2+ overload
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Zhou, Q., Yang, J., Wang, W., Shao, C., Hua, X., & Tang, Y. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01908-2 · Cited by 81
Relationship between stress hyperglycaemic ratio (SHR) and critical illness: a systematic review
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ER membranes associated with mitochondria: Possible therapeutic targets in heart-associated diseases
Silva‐Palacios, A., Zazueta, C., & Pedraza‐Chaverrí, J. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104758 · Cited by 74
Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation：novel therapeutic targets for neurodegenerative diseases.
He, Q., Qu, M., Shen, T., Su, J.-K., Xu, Y., Xu, C.-Y., Barkat, M., Cai, J.-B., Zhu, H.-B., Zeng, L.-H., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101920 · Cited by 75
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Li, A., Lian, L., Chen, X.-N., Cai, W.-H., Fan, X., Fan, Y.-J., Li, T., Xie, Y., & Zhang, J. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.08.009 · Cited by 67
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Li, J., Zhang, D., Brundel, B. J. J. M., & Wiersma, M. (2019) · Cells · doi:10.3390/cells8121617 · Cited by 55
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Wang, X., Zhang, X., Cao, K. J., Zeng, M., Fu, X., Zheng, A., Zhang, F., Gao, F., Zou, X., Li, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31548-1 · Cited by 58
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Hernández‐Reséndiz, S., Prakash, A., Loo, S. J., Semenzato, M., Chinda, K., Crespo-Avilan, G. E., Dam, L. C., Lu, S., Scorrano, L., & Hausenloy, D. J. (2023) · Basic Research in Cardiology · doi:10.1007/s00395-023-01019-9 · Cited by 57
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Li, Y., Li, H., Shao, J., Zhu, L., Xie, T., Cai, J., Wang, W., Cai, M.-X., Wang, Z., Yao, Y., et al. (2022) · Biomolecules · doi:10.3390/biom12121778 · Cited by 47
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Zhang, L., Wang, Y., Ju, J., Shabanova, A., Li, Y., Fang, R., Sun, J., Guo, Y., Jin, T., Liu, Y., et al. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0489-0 · Cited by 42
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Xie, S., Zhang, M., Shi, W., Xing, Y., Huang, Y. Q., Fang, W., Liu, S., Chen, M., Zhang, T., Chen, S., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.026728 · Cited by 42
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Zhong, W., Wang, X., Yang, L., Wang, Y., Xiao, Q., Yu, S., Cannon, R. D., Bai, Y., Zhang, C., Chen, D., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c08146 · Cited by 40
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de Giusti, C. J., Palomeque, J., & MATTIAZZI, A. R. (2022) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-021-02650-y · Cited by 35
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Zou, F., Wang, L., Liu, H., Wang, W., Hu, L., Xiong, X., Wu, L., Shen, Y., & Yang, R. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01219 · Cited by 33
Mitochondria-associated endoplasmic reticulum membranes in the heart
Wu, S., & Zou, M. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.12.018 · Cited by 33
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Dubois, M., Boulghobra, D., Rochebloine, G., Pallot, F., Yehya, M., Bornard, I., Gayrard, S., Coste, F., Walther, G., Meyer, G., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103044 · Cited by 33
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Xu, H., Yu, W., Sun, M., Bi, Y., Wu, N. N., Zhou, Y., Yang, Q., Zhang, M., Ge, J., Zhang, Y., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155551 · Cited by 30
New therapeutic directions in type II diabetes and its complications: mitochondrial dynamics
Wang, S., Zhao, H., Lin, S., Lv, Y., Lin, Y. N., Liu, Y., Peng, R., & Jin, H. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1230168 · Cited by 33
Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets
Ye, W., Han, K., Xie, M., Li, S., Chen, G., Wang, Y., & Li, T. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003075 · Cited by 32

Authors: Wu, S., Lu, Q., Ding, Y., Wu, Y., Qiu, Y., Wang, P., Mao, X., Huang, K., Xie, Z., & Zou, M.-H.
Affiliations: Georgia State University (US)
University of Washington (US)
Wuhan Union Hospital (CN)
Corresponding author: Xie, Zhonglin
Zou, Ming-Hui
ORCID: Wu, Shengnan
Lu, Qiulun
Ding, Ye
Wu, Yin
Wang, Pei
Mao, Xiaoxiang
Huang, Kai
Zou, Ming-Hui
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2019-04-16
Volume: 139
Issue: 16
Pages: 1913-1936
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.118.033552
PMC: PMC6465113
OpenAlex: W2911037090
Semantic Scholar: 6ae43efb25ca95c487961d8441dedd8e60e67291
Cited by: 298
References: 78
Citations by year: 2026: 37 · 2025: 48 · 2024: 55 · 2023: 43 · 2022: 47 · 2021: 27 · 2020: 32 · 2019: 8
FWCI: 9.43
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association (16POST31160009, 16GRANT29590003, 16POST29960011)
University of Washington
Georgia Research Alliance
National Institute on Aging (AG047776, R01AG047776)
National Heart, Lung, and Blood Institute (HL128014, HL137371, R01HL105157, HL 079584, R01HL079584, HL110488, HL140954, HL-080499, R01HL142287, R01HL137371, R01HL132500, R01HL074399, R01HL080499, HL132500, HL-089920, R01HL140954, R01HL110488, HL142287, R01HL128014, R01HL089920, CA213022, R01HL096032)
National Cancer Institute (CA-213022, R01CA213022)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords: diabetic cardiomyopathy, hyperglycemia, FUNDC1, mitochondria-associated endoplasmic reticulum membranes, IP3R2, mitochondrial calcium flux, mitophagy, AMPK, mitochondrial dysfunction, cardiomyocytes, streptozotocin-induced diabetes, Akita mice, cardiomyocyte-specific knockout, apoptosis, mitochondrial fragmentation, ubiquitination
MeSH terms: Adult, Aged, Animals, Cell Line, Endoplasmic Reticulum, Female, Gene Expression Regulation, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Middle Aged, Mitochondria, Myocardial Contraction, Mice, Knockout, Calcium Signaling, Mitochondrial Proteins, Myocytes, Cardiac, Mitochondrial Membranes, Mice, Rats, AMP-Activated Protein Kinases, Diabetic Cardiomyopathies

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Hyperglycemia-Driven Inhibition of AMP-Activated Protein Kinase α2 Induces Diabetic Cardiomyopathy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes In Vivo

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