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PGC-1 coactivators in the cardiovascular system
IS Patten... - Trends in Endocrinology & Metabolism, 2011 - Elsevier The beating heart consumes more ATP per weight than any other organ. The machineries required for this are many and complex. Fuel and oxygen must be transported via the vasculature, absorbed by cardiomyocytes, broken down, and regulated to match cellular ...
Figure 1. PGC-1s as orchestrators. PGC-1s activate gene expression in the nucleus to regulate broad programs of mitochondrial biology and ancillary programs relevant to mitochondrial biology. Genes encoding proteins and processes indicated in red are targets of PGC-1s. GLUT4 and CD36 facilitate entry of fuels into the cell, whereas CPT1 and PDH transport activated fuel into mitochondria. β-Oxidation of fat yields acetyl Co A that enters the Krebs cycle, yielding reducing equivalents that can donate electrons to the electron complex chain, ultimately converting ADP to ATP. ANT exports ATP to the cytoplasm, where the creatine shuttle (C Kmito and C Kmm) facilitates the transport of high-energy phosphate bonds to the myofibril, a primary site of ATP consumption. The secretion of the potent angiogenic factor VEGF stimulates neovascularization, increasing the capacity of the vascular network to sustain high flux of fuels to the myocyte and its mitochondria. Byproducts of mitochondrial respiration include ROS, which can be scavenged by enzymes such as SOD2 and catalase. Mitochondrial biogenesis itself requires replication of the mitochondrial genome, via TFAM and TFB1/2, whereas mitochondrial homeostasis involves constant fusion and fission.
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