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The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats.
- Source :
-
Communications biology [Commun Biol] 2020 Jul 17; Vol. 3 (1), pp. 389. Date of Electronic Publication: 2020 Jul 17. - Publication Year :
- 2020
-
Abstract
- Mitochondrial dysfunction contributes to cardiac pathologies. Barriers to new therapies include an incomplete understanding of underlying molecular culprits and a lack of effective mitochondria-targeted medicines. Here, we test the hypothesis that the cardiolipin-binding peptide elamipretide, a clinical-stage compound under investigation for diseases of mitochondrial dysfunction, mitigates impairments in mitochondrial structure-function observed after rat cardiac ischemia-reperfusion. Respirometry with permeabilized ventricular fibers indicates that ischemia-reperfusion induced decrements in the activity of complexes I, II, and IV are alleviated with elamipretide. Serial block face scanning electron microscopy used to create 3D reconstructions of cristae ultrastructure reveals that disease-induced fragmentation of cristae networks are improved with elamipretide. Mass spectrometry shows elamipretide did not protect against the reduction of cardiolipin concentration after ischemia-reperfusion. Finally, elamipretide improves biophysical properties of biomimetic membranes by aggregating cardiolipin. The data suggest mitochondrial structure-function are interdependent and demonstrate elamipretide targets mitochondrial membranes to sustain cristae networks and improve bioenergetic function.
- Subjects :
- Animals
Hydrogen Peroxide metabolism
Male
Mass Spectrometry
Microscopy, Electron, Transmission
Mitochondria, Heart metabolism
Mitochondria, Heart ultrastructure
Mitochondrial Membranes drug effects
Mitochondrial Membranes ultrastructure
Rats
Rats, Sprague-Dawley
Cardiolipins metabolism
Cardiotonic Agents therapeutic use
Myocardial Reperfusion Injury drug therapy
Oligopeptides therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 3
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 32680996
- Full Text :
- https://doi.org/10.1038/s42003-020-1101-3