Making ROS for apoptosis

Reactive oxygen species (ROS) are not all accidental and unwanted byproducts. Marco Giorgio, Enrica Migliaccio, Pier Giuseppe Pelicci (University of Milan, Italy), and colleagues report that a protein called p66^Shc purposely siphons electrons from the respiratory chain and uses them to trigger apoptosis during times of stress.

Cells that lack p66^Shc were known to produce less ROS and be resistant to various pro-apoptosis stimuli. Giorgio et al. now show that p66^Shc is sufficient to induce mitochondrial swelling and rupture when added to purified mitochondria. The protein also induces excess ROS production, but only when the organelles are undergoing respiration.p66^Shc takes electrons from the respiratory protein cytochrome c and uses them to produce the ROS hydrogen peroxide. p66^Shc diverts only a fraction of the electrons though, and respiration continues in its presence.

Because hydrogen peroxide can diffuse through the mitochondria and open holes in the membrane, p66^Shc's redirection of electrons must somehow be regulated to prevent unwanted apoptosis. p66^Shc increases production of ROS during times of stress, when cellular damage might be too extensive to repair. But just how the cell limits p66^Shc activity during healthy times is not yet clear.

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