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Novel Dual-Fluorescent Mitophagy Reporter Reveals a Reduced Mitophagy Flux in Type 1 Diabetic Mouse Heart

Journal: The Journal of the American Osteopathic Association Date: 2020/07, 120(7):Pages: 446-455. doi: Subito , type of study: Base

Free full text   (https://www.degruyter.com/document/doi/10.7556/jaoa.2020.072/html)

Keywords:

diabetes [29]
heart failure [12]
mitochrondria [1]
mitochondrial autophagy [1]
mitophagy [1]
baseline study [22]

Abstract:

CONTEXT: Patients with diabetes are susceptible to heart failure. Defective mitochondria can cause cardiac damage. Mitochondrial autophagy or mitophagy is a quality control mechanism that eliminates dysfunctional mitochondria through lysosome degradation. Mitophagy is essential for maintaining a pool of healthy mitochondria for normal cardiac function. However, the effect of diabetes on the functional status of cardiac mitophagy remains unclear. OBJECTIVE: To determine and compare cardiac mitophagy flux between diabetic and nondiabetic mice. METHODS: Using a novel dual fluorescent mitophagy reporter termed mt-Rosella, we labeled and traced mitochondrial fragments that are sequestered by the autophagosome and delivered to and degraded in the lysosome. RESULTS: Mitophagic activity was reduced in high-glucose-treated cardiomyocytes and in the heart tissue of type 1 diabetic mice. CONCLUSIONS: Mitophagy was impaired in the heart of diabetic mice, suggesting that restoring or accelerating mitophagy flux may be a useful strategy to reduce cardiac injury caused by diabetes.


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