Diabetes increases the vulnerability of the cardiac mitochondrial network to criticality

• Verfasst von: Vetter, Larissa [VerfasserIn]
• Verfasst von: Cortassa, Sonia [VerfasserIn]
• Verfasst von: O’Rourke, Brian [VerfasserIn]
• Verfasst von: Armoundas, Antonis A. [VerfasserIn]
• Verfasst von: Bedja, Djahida [VerfasserIn]
• Verfasst von: Jende, Johann [VerfasserIn]
• Verfasst von: Bendszus, Martin [VerfasserIn]
• Verfasst von: Paolocci, Nazareno [VerfasserIn]
• Verfasst von: Sollot, Steven J. [VerfasserIn]
• Verfasst von: Aon, Miguel A. [VerfasserIn]
• Verfasst von: Kurz, Felix T. [VerfasserIn]
• Titel: Diabetes increases the vulnerability of the cardiac mitochondrial network to criticality
• Verf.angabe: 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
• E-Jahr: 2020
• Jahr: 10 March 2020
• Umfang: 12 S.
• Fussnoten: Gesehen am 14.01.2021
• Titel Quelle: Enthalten in: Frontiers in physiology
• Ort Quelle: Lausanne : Frontiers Research Foundation, 2007
• Jahr Quelle: 2020
• Band/Heft Quelle: 11(2020) Artikle-Nummer 175, 12 Seiten
• ISSN Quelle: 1664-042X
• DOI: doi:10.3389/fphys.2020.00175
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cardiac myocyte
• Sach-SW: Mitochondria
• Sach-SW: mitochondrial criticality
• Sach-SW: type 1 diabetes
• Sach-SW: wavelet analysis
• K10plus-PPN: 174467521X

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.