Diabetes Increases the Vulnerability of the Cardiac Mitochondrial Network to Criticality

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, Felix T. Kurz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number175
JournalFrontiers in Physiology
Volume11
DOIs
StatePublished - Mar 10 2020

Keywords

  • cardiac myocyte
  • mitochondria
  • mitochondrial criticality
  • type 1 diabetes
  • wavelet analysis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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