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

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.