Cardiopulmonary MedicineORIGINAL ARTICLE

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

Satoru Kobayashi, PhD; Joy Patel, BS; Fengyi Zhao, MD; Yuan Huang, MD; Tamayo Kobayashi, MS; and Qiangrong Liang, MD, PhD
Notes and Affiliations
Notes and Affiliations

Received: August 24, 2019

Accepted: September 18, 2019

Published: July 1, 2020

J Osteopath Med; 120(7): 446-455

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.

Objectives: 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.

Read Full Article