Deciphering a novel kinase function for adck2 in the heart

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Project Summary Heart failure (HF) is a leading cause of death in the world characterized by progressive heart disease that affects the pumping action of the heart muscle. As the heart is a mechanical pump solely responsible to distribute oxygenated blood to peripheral organs, discovering novel mechanisms that allow for this highly energetic organ to fulfill its function is vital for understanding basic molecular and cellular mechanisms and physiology in heart cells in normal and pathologic conditions. Mitochondria are the main drivers for ATP generation, thus these cellular structures set the energetic potential of heart cells to ultimate supply the demand for contractile generation. ADCK2, is an uncharacterized aarF domain containing kinase 2, highly expressed in the heart. Computationally, it has been predicted to enable ATP binding activity and be involved in ubiquinone biosynthesis (coenzyme Q). In addition, STRING interaction network analysis positions ADCK2 as an interactor with scl25a5 (ANT2) and TIMM13 (a member of the mitochondrial transport system). While computational evidence points to an important role for this kinase in the heart, little is known about this kinase. This project aims at filling in this gap in knowledge. We hypothesize that indeed ADCK2 is important for cardiac mitochondrial function in the adult heart, particularly involving the potential role in CoQ and electron transport chain function. Data originated from this project will serve as the basis for expansion into other larger studies. Two main aims are proposed in this relatively small study: 1) Determining the role of ADCK2 in mitochondrial respiration and adult cardiomyocyte substrate utilization; 2) Exploring how loss of ADCK2 in the heart alter ATP generation and cell survival. The overarching goal of this project is to generate tools and initial data that will engage future studies on this unexplored yet promising kinase.