Posts Tagged: cell cycle

Multimodal Regulation of Cardiac Myocyte Proliferation

Multimodal Regulation of Cardiac Myocyte Proliferation

Xuejun Yuan, Thomas Braun

Schematic overview of cell-cycle activities, global DNA methylation, and metabolic properties of fetal, neonatal, adult, and hypertrophic cardiac myocytes. Green arrows represent cell-cycle processes leading to endomitosis and multinucleation, whereas orange arrows refer to endoreduplication resulting in polyploidy. cTnI (TNNI3) indicates cardiac troponin; FAO, fatty acid oxidation; and ssTnI(TNNI1), slow skeletal troponin. [Powerpoint File]

Multimodal Regulation of Cardiac Myocyte Proliferation

Multimodal Regulation of Cardiac Myocyte Proliferation

Xuejun Yuan, Thomas Braun

Schematic overview of the potential interplay between metabolic signals and epigenetic mechanisms for regulation of cardiac myocyte proliferation. Oxygen-dependent stimulation of mitochondrial respiration increases α-ketoglutarate (α-KG) production, which might stimulate DNA and histone demethylation thereby activating anti-proliferative genes or inducing accumulation of intracellular reactive oxygen species (ROS) and DNA damage responses. Such cues might promote polyplodization and/or activation of Hippo signaling prompting cell-cycle exit. In contrast, hypoxia stabilizes HIF1α (hypoxia-inducible factor 1-alpha) and leads to accumulation of intermediate metabolites such as succinate and fumarate, which inhibit α-KG–dependent epigenetic modifiers including TETs (ten–eleven translocation) and histone demethylases (HDMs) and stabilize HIF1α thus activating proproliferative gene programs. In addition, fumarate activates the Nrf2/Pitx2/Yap1 axis, which positively regulates proproliferative gene programs. Dashed lines indicate regulatory cascades investigated in noncardiac myocytes. [Powerpoint File]