Mitochondrial dynamics in the heart (234.1)

Although the mammalian heart is the most mitochondrial‐rich organ, adult cardiac myocytes are notable for absence of interconnected mitochondrial networks and paucity of mitochondrial dynamism that typically remodels such networks in other cell types. Nevertheless, proteins whose conventional function is to remodel mitochondrial structure through organelle fission and fusion are highly expressed in mammalian hearts. Using conditional gene manipulation of pro‐fusion mitofusins and pro‐fission Drp‐1 in cultured cells, Drosophila heart tubes, and mouse hearts, our laboratory identified non‐canonical functions for mitochondrial dynamics proteins central to maintenance of metabolic cardiac homeostasis through mitochondrial quality control. In this talk I will review recent work that uncovered mechanisms of interactive molecular cross‐talk between mitochondrial fission/fusion and mitophagy pathways, thus establishing the interdependence of these two processes. Using experimental cardiac‐specific Parkin dysfunction as a model system of mitophagic dysfunction, the therapeutic potential of approaches aimed at restoring the balance between fission/fusion on the one hand and mitophagy on the other will be examined.