Formation of highly organized intracellular structure and energy metabolism in cardiac muscle cells during postnatal development of rat heart

Abstract

Adult cardiomyocytes have highly organized intracellular structure and energy metabolism whose formation during postnatal development is still largely unclear. Our previous results together with the data from the literature suggest that cytoskeletal proteins, particularly βII-tubulin, are involved in the formation of complexes between mitochondria and energy consumption sites. The aim of this study was to examine the arrangement of intracellular architecture parallel to the alterations in regulation of mitochondrial respiration in rat cardiomyocytes during postnatal development, from 1 day to 6 months. Respirometric measurements were performed to study the developmental alterations of mitochondrial function. Changes in the mitochondrial arrangement and cytoarchitecture of βII- and αIV-tubulin were examined by confocal microscopy. Our results show that functional maturation of oxidative phosphorylation in mitochondria is completed much earlier than efficient feedback regulation is established between mitochondria and ATPases via creatine kinase system. These changes are accompanied by significant remodeling of regular intermyofibrillar mitochondrial arrays aligned along the bundles of βII-tubulin. Additionally, we demonstrate that formation of regular arrangement of mitochondria is not sufficient per se to provide adult-like efficiency in metabolic feed-back regulation, but organized tubulin networks and reduction in mitochondrial outer membrane permeability for ADP are necessary as well. In conclusion, cardiomyocytes in rat heart become mature on the level of intracellular architecture and energy metabolism at the age of 3 months.

Development of endothermy and concomitant increases in cardiac and skeletal muscle mitochondrial respiration in the precocial Pekin duck (Anas platyrhynchos domestica)

“…These changes would likely require greater work from the ventricles, which would necessitate a greater OXPHOS capacity. Increases in cardiomyocyte OXPHOS capacity after birth have been observed in neonatal rats (Anmann et al, 2014). In contrast, there is little change in OXPHOS capacity of the ectothermic alligator and snapping turtle cardiomyocytes upon hatching, as expected in species that do not transition to an endothermic phenotype .…”

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

“…Further, tethering to tubulin, actin [64], and intermediate filaments [65] is required for mitochondrion cristae to acquire their characteristics invaginated morphology. Tubulin tethering to mitochondria has been shown to play both structural and functional roles in striated muscle homeostasis [66] and disease [10]. Specifically, by physically and chemically interacting with the mitochondrial outer membrane, tubulin modulates the function of the permeability transition pore [67] and of voltage-dependent anion channels [68].…”

“…This creates a functional microdomain, termed the intracellular energetic unit (ICEU), where rapid catabolism drives a chemical gradient of ATP from the mitochondria to the sarcoplasmic reticulum and sarcomeres [9, 10]. Here, we first review some recent results suggesting a link between the cell microenvironment, the contractile cytoskeleton, and metabolism, which we hypothesize to interact at the level of intracellular energetic units.…”

The location of energetic compartments affects energetic communication in cardiomyocytes

“…Likewise, neonatal mammals with lower cardiac performance and higher reliance on glycolysis do not express Mi-CK (Hoerter et al, 1991, 1994; Tiivel et al, 2000). As the cardiomyocytes mature, they increase in diameter and develop from a relatively simple morphology to multiple parallel rows of myofibrils and mitochondria organized in a crystal-like pattern as we know it in adult cardiomyocytes (Vendelin et al, 2005; Birkedal et al, 2006; Anmann et al, 2014). In parallel, they develop t-tubules and a more elaborate SR (Sedarat et al, 2000; Dan et al, 2007) as their excitation contraction coupling changes to depend less on trans sarcolemmal Ca 2+ -transport and more on L-type Ca 2+ -influx to trigger Ca 2+ -release from the SR (Huang et al, 2008).…”

“…In mammal heart, the SR develops significantly postnatally (Dan et al, 2007; Huang et al, 2008), and so does its association with mitochondria (Boncompagni et al, 2009). Thus, changes in SR-mitochondria interactions might provide an alternative explanation for the inter-species differences and developmental changes in the apparent ADP-affinity of permeabilized cardiomyocytes (Ventura-Clapier et al, 1998; Sokolova et al, 2009; Anmann et al, 2014). Additionally, the low apparent ADP-affinity is specific for oxidative muscles (Kuznetsov et al, 1996; Ventura-Clapier et al, 1998).…”