fig5

Figure 5. Proteins involved in mitochondrial unfolded protein response (UPR^mt) activation and regulation by MERCs in cardiac aging. Convergence between the endoplasmic reticulum (ER)-mitochondria-nucleus organelles maintains cellular homeostasis. Thus, dysfunction of this communion is intimately associated with the development of cardiovascular disease (CVDs) during aging. In particular, tie proteins (LonP1 and Sirt1) enhance communication between mitochondria-RE contact sites (MERCs), both of which are nuclear-encoded and subsequently translated, identified, distributed, and inserted as anchor proteins between MERCs. Overexpression of Sirt1 and LonP1 increases MERCs and, in parallel, activates UPR^mt. SIRT1 regulates energy homeostasis, promotes mitohormesis, and prevents ER stress, whereas LonP1 decreases mitochondrial fragmentation, activates the unfolded protein response of endoplasmic reticulum unfolded protein response (UPR^RE), maintains mitochondrial integrity, and decreases oxidative damage. Created using BioRender (www.app.biorender.com).