Abstract: PO0923
Loxl4 Deacetylates OPA1 to Regulate Mitochondrial Dynamics During Diabetes
Session Information
- Diabetic Kidney Disease: Basic Mechanisms
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Ke, Qingqing, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiang, Lei, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Zhou, Yang, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Yang, Junwei, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Background
Mitochondrial morphology is regulated by the balance between two counteracting mitochondrial processes of fusion and fission. There is significant evidence suggesting a stringent association between morphology and bioenergetics of mitochondria. Morphological alterations in mitochondria are linked to several pathological disorders, including diabetic kidney disease. The consequences of high glucose-induced acetylation of mitochondrial proteins on the organelle morphology and function remain largely unexplored.
Methods
Here, we examined the kidneys of mice with streptozotocin-induced diabetes and primary tubular epithelial cells exposed to high glucose.
Results
Using high-resolution mass spectrometry, we identified 152 hyperacetylated and 19 hypoacetylated proteins in the mitochondria from kidney tubule of diabetic mice compared with control mice. OPA1, a mitochondrial fusion protein was hyperacetylated at lysine 228, 792 and 847 residuals under high glucose-induced pathological stress and this posttranslational modification increased mitochondrial fragmentation. Overexpression of a deacetylation-mimetic version of OPA1 recovered the mitochondrial functions of OPA1-null cells, thus demonstrating the functional significance of K228/792/847 acetylation in regulating OPA1 activity. The newly discovered deacetylase lysyl oxidase like 4 (Loxl4) interacts with OPA1 in mitochondria. Overexpression of Loxl4 prevents high glucose-induced acetylation, preserved mitochondrial networking and protected the high glucose-induced decrease of oxygen consumption rate.
Conclusion
In summary, these data indicated that hyperacetylation of OPA1 regulates mitochondrial fusion and fission under diabetes conditions. Loxl4 promotes mitochondrial function by regulating mitochondrial dynamics by targeting OPA1.
Funding
- Government Support - Non-U.S.