Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes
Open accessAbstract
AIMS/HYPOTHESIS: Mitochondria frequently change their shapes by fusion and fission and these morphological dynamics play important roles in mitochondrial function and development as well as programmed cell death. The goal of this study is to investigate whether: (1) mitochondria in mouse coronary endothelial cells (MCECs) isolated from diabetic mice exhibit increased fragmentation; and (2) chronic treatment with a superoxide anion (O(2)(-)) scavenger has a beneficial effect on mitochondrial fragmentation in MCECs. METHODS: MCECs were freshly isolated and lysed for protein measurement, or cultured to determine mitochondrial morphology and O(2)(-) production. For the ex vivo hyperglycaemia experiments, human coronary endothelial cells were used. RESULTS: Elongated mitochondrial tubules were observed in MCECs isolated from control mice, whereas mitochondria in MCECs from diabetic mice exhibited augmented fragmentation. The level of optic atrophy 1 (OPA1) protein, which leads to mitochondrial fusion, was significantly decreased, while dynamin-related protein 1 (DRP1), which leads to mitochondrial fission, was significantly increased in MCECs from diabetic mice. Diabetic MCECs exhibited significantly higher O(2)(-) concentrations in cytosol and mitochondria than control MCECs. Administration of the O(2)(-) scavenger TEMPOL to diabetic mice for 4 weeks led to a significant decrease in mitochondrial fragmentation without altering the levels of OPA1 and DRP1 proteins in MCECs. High-glucose treatment for 24 h significantly induced mitochondrial fragmentation, which was restored by TEMPOL treatment. In addition, excess O(2)(-) production, either in cytosol or in mitochondria, significantly increased mitochondrial fragmentation. CONCLUSIONS/INTERPRETATION: These data suggest that lowering the O(2)(-) concentration can restore the morphological change in mitochondria and may help improve mitochondrial function in diabetic MCECs.
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Mitochondrial fragmentation is present in coronary endothelial cells from diabetic mice.
“Another study revealed mitochondrial fragmentation in coronary endothelial cells from diabetic mice (26).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [26]
Many studies demonstrated effect of hyperglycemia on increased generation of ROS and mitochondrial fission in a variety of cell types.
“Although many studies demonstrated the effect of hyperglycemia on increased generation of ROS and mitochondrial fission in a variety of cell types (26, 48), elevated circulating lipid and inflammatory cytokines usually occur prior to the development of hyperinsulinemia and hyperglycemia during the progression of type 2 diabetes (27, 38).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [26]
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- Authors
- Makino, A., Scott, B. T., & Dillmann, W. H.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Dillmann, W. H.
- Venue
- Diabetologia
- Published
- 2010-05-13
- Volume
- 53
- Issue
- 8
- Pages
- 1783-1794
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC2892085
- OpenAlex
- W2146173783
- Cited by
- 223
- References
- 52
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 16 · 2022: 15 · 2021: 15 · 2020: 21 · 2019: 15 · 2018: 18 · 2017: 15 · 2016: 14 · 2015: 8 · 2014: 17 · 2013: 9 · 2012: 16
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Diabetologia (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (MD00220)
- National Heart, Lung, and Blood Institute (HL-66917, R01HL066917)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-083506, K01DK083506)
- National Institute on Minority Health and Health Disparities (P60MD000220, MD00220)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- mitochondrial fragmentation, superoxide, coronary artery endothelial cells, type 1 diabetes, mitochondrial fission, mitochondrial fusion, OPA1, Drp1, tempol, superoxide scavengers, high glucose, mitochondrial morphology, diabetic cardiomyopathy
- MeSH terms
- Animals, Antioxidants, Cells, Cultured, Cyclic N-Oxides, Diabetes Mellitus, Type 1, Endothelium, Vascular, Glucose, Membrane Fusion, Mitochondria, Myocardium, Spin Labels, Superoxides, Blotting, Western, Dinoprostone, Oxidative Stress, Isoprostanes, Endothelial Cells, Mice
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