Role for Bcl-x(L) as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis

Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-2-related protein Bcl-x(L) fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress. Coimmunoprecipitation studies demonstrate that Bcl-x(L) associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-x(L) and not to the proapoptotic Bcl-x(s) protein. The results also demonstrate that Bcl-x(s) blocks binding of cytochrome C to Bcl-x(L). Our findings support a role for Bcl-x(L) in protecting cells from apoptosis by inhibiting the availability of cytochrome C in the cytosol.