Caveolae-associated signaling toward mitochondria contributes to the cardioprotective mechanisms against ischemia-reperfusion (I/R) injury induced by ischemic postconditioning.In this work, we evaluated the role that the actin-cytoskeleton network exerts on caveolae-mitochondria communication during postconditioning.Isolated rat hearts skateboards subjected to I/R and to postconditioning were treated with latrunculin A, a cytoskeleton disruptor.
Cardiac function was compared between these hearts and those exposed only to I/R and to the cardioprotective maneuver.Caveolae and mitochondria structures were determined by electron microscopy and maintenance of the actin-cytoskeleton was evaluated by phalloidin staining.Caveolin-3 and other putative caveolae-conforming proteins were detected by immunoblot analysis.
Co-expression of caveolin-3 and actin was evaluated both in lipid raft fractions and in heart tissue from the different groups.Mitochondrial function was assessed by respirometry and correlated with cholesterol levels.Treatment with latrunculin A abolishes the cardioprotective postconditioning effect, inducing morphological and structural changes in cardiac tissue, reducing F-actin staining and diminishing caveolae formation.
Latrunculin A administration to post-conditioned hearts decreases the interaction between caveolae-forming proteins, the co-localization of caveolin with actin and inhibits Bangers oxygen consumption rates in both subsarcolemmal and interfibrillar mitochondria.We conclude that actin-cytoskeleton drives caveolae signaling to mitochondria during postconditioning, supporting their functional integrity and contributing to cardiac adaption against reperfusion injury.