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).
Patergnani et al. Cell Communication and Signaling 2011 9:19 doi:10.1186/1478-811X-9-19