The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats.

Communications Biology
Mitchell E AllenSaame Raza Shaikh

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 s...Continue Reading

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Citations

Sep 21, 2020·The British Journal of Ophthalmology·Alan Bird
Apr 13, 2021·Frontiers in Endocrinology·Ugochukwu Kelvin IhenachoR Blake Hill
May 6, 2021·Pharmacology Research & Perspectives·Joseph JohnsonHong Lin
Sep 13, 2021·The FEBS Journal·Christopher F BennettPere Puigserver
Oct 30, 2021·Journal of Inherited Metabolic Disease·Reid ThompsonHilary J Vernon

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Methods Mentioned

BETA
transmission electron microscopy
electron microscopy
scanning electron microscopy

Software Mentioned

ImageJ
GraphPad Prism

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