P2X7 is a bifunctional receptor (P2X7R) for extracellular ATP that, depending on the level of activation, forms a cation-selective channel or a large conductance non-selective pore. The P2X7R has a strong pro-apoptotic activity but also promotes cell survival in the absence of serum. To clarify this dual role of the receptor we investigated the behavior of mitochondria, which are organelles central to determine both cell survival and death, in P2X7 transfected HEK cells. Transfection of P2X7R increases resting mitochondrial potential (mt), basal mitochondrial Ca2+ ([Ca2+]mt) and intracellular ATP content. Accordingly, P2X7 transfectants acquire an advantage to grow in serum-free medium. These changes depend on an autocrine/paracrine tonic stimulation by secreted ATP. On the other hand, sustained stimulation of P2X7R causes a mt drop, a large increase in [Ca2+]mt, mitochondrial fragmentation and cell death. Both the growth-promoting and the death-inducing responses are abolished in cells transfected with a mutated P2X7 receptor unable to form the non-selective pore. Thus, whether P2X7 activation has a death-inducing or survival-promoting effect is strictly dependent on mitochondrial structure and function.
P2X7 DEPENDENT PROLIFERATION AND APOPTOSIS: A MITOCHONDRIAL AFFAIR.
ADINOLFI, Elena;CALLEGARI, Maria Giulia;FERRARI, Davide;PINTON, Paolo;RIZZUTO, Rosario;DI VIRGILIO, Francesco
2005
Abstract
P2X7 is a bifunctional receptor (P2X7R) for extracellular ATP that, depending on the level of activation, forms a cation-selective channel or a large conductance non-selective pore. The P2X7R has a strong pro-apoptotic activity but also promotes cell survival in the absence of serum. To clarify this dual role of the receptor we investigated the behavior of mitochondria, which are organelles central to determine both cell survival and death, in P2X7 transfected HEK cells. Transfection of P2X7R increases resting mitochondrial potential (mt), basal mitochondrial Ca2+ ([Ca2+]mt) and intracellular ATP content. Accordingly, P2X7 transfectants acquire an advantage to grow in serum-free medium. These changes depend on an autocrine/paracrine tonic stimulation by secreted ATP. On the other hand, sustained stimulation of P2X7R causes a mt drop, a large increase in [Ca2+]mt, mitochondrial fragmentation and cell death. Both the growth-promoting and the death-inducing responses are abolished in cells transfected with a mutated P2X7 receptor unable to form the non-selective pore. Thus, whether P2X7 activation has a death-inducing or survival-promoting effect is strictly dependent on mitochondrial structure and function.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
