title: Mechanotransduction and Metabolism in Cardiomyocyte Microdomains.
abstract: Efficient contractions of the left ventricle are ensured by the continuous transfer of adenosine triphosphate (ATP) from energy production sites, the mitochondria, to energy utilization sites, such as ionic pumps and the force-generating sarcomeres. To minimize the impact of intracellular ATP trafficking, sarcomeres and mitochondria are closely packed together and in proximity with other ultrastructures involved in excitation-contraction coupling, such as t-tubules and sarcoplasmic reticulum junctions. This complex microdomain has been referred to as the intracellular energetic unit. Here, we review the literature in support of the notion that cardiac homeostasis and disease are emergent properties of the hierarchical organization of these units. Specifically, we will focus on pathological alterations of this microdomain that result in cardiac diseases through energy imbalance and posttranslational modifications of the cytoskeletal proteins involved in mechanosensing and transduction.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Institute for Regenerative Medicine (IREM), Wyss Translational Center, University and ETH Zurich, Zurich, Switzerland.
authors.forename: Francesco S
authors.identifier: 0000-0001-7038-3121
authors.initials: FS
authors.lastname: Pasqualini
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Nesmith
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; James Worth Bagley College of Engineering and College of Agriculture and Life Sciences, Mississippi State University, Starkville, MS, USA.
authors.forename: Renita E
authors.initials: RE
authors.lastname: Horton
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sheehy
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D056966:Excitation Contraction Coupling / Q000502:physiology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology