Diabetes increases the vulnerability of the cardiac mitochondrial network to criticality
Mitochondrial criticality describes a state in which the mitochondrial cardiac network under intense oxidative stress becomes very sensitive to small perturbations, leading from local to cell-wide depolarization and synchronized oscillations that may escalate to the myocardial syncytium generating a...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 March 2020
|
| In: |
Frontiers in physiology
Year: 2020, Volume: 11 |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2020.00175 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fphys.2020.00175 Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fphys.2020.00175/full 
|
| Author Notes: | Larissa Vetter, Sonia Cortassa, Brian O’Rourke, Antonis A. Armoundas, Djahida Bedja, Johann M. E. Jende, Martin Bendszus, Nazareno Paolocci, Steven J. Sollot, Miguel A. Aon and Felix T. Kurz |
| Summary: | Mitochondrial criticality describes a state in which the mitochondrial cardiac network under intense oxidative stress becomes very sensitive to small perturbations, leading from local to cell-wide depolarization and synchronized oscillations that may escalate to the myocardial syncytium generating arrhythmias. Herein, we describe the occurrence of mitochondrial criticality in the chronic setting of a metabolic disorder, type 1 diabetes (T1DM), using a streptozotocin (STZ)-treated guinea pig (GP) animal model. Using wavelet analysis of mitochondrial networks from two-photon microscopy imaging of cardiac myocytes loaded with a fluorescent probe of the mitochondrial membrane potential, we show that cardiomyocytes from T1DM GPs are closer to criticality, making them more vulnerable to cell-wide mitochondrial oscillations as can be judged by the latency period to trigger oscillations after a laser flash perturbation, and their propensity to oscillate. Insulin treatment of T1DM GPs rescued cardiac myocytes to sham control levels of susceptibility, a protective condition that could also be attained with interventions leading to improvement of the cellular redox environment such as preincubation of diabetic cardiac myocytes with the lipid palmitate or a cell-permeable form of glutathione, in the presence of glucose. |
|---|---|
| Item Description: | Gesehen am 14.01.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2020.00175 |