Figure 2

PML and p66Shc regulates cell span at the MAMs level. The tumor suppressor PML in resting conditions resides in a specific multi-protein complex with IP3R, PP2a and AKT, essential for a normal Ca²⁺ flux from ER to mitochondria and, consequently, for correct apoptosis levels (upper panel). Aging and ROS determine phosphorylation and accumulation of p66Shc in the MAMs fraction. The presence of phospho-p66Shc at the mitochondrial level determines alterations in mitochondrial homeostasis, including Ca²⁺ signalling, and ultimately increases apoptotic and senescence responses (lower panel).