Which types of signals can initiate apoptosis?

• A. Extracellular (extrinsic) and intracellular (intrinsic) signals can initiate apoptosis.
• B. Only extracellular signals initiate apoptosis.
• C. Intracellular signals initiate apoptosis exclusively.
• D. Apoptosis is independent of signaling.

Answer: (B)

Apoptosis can be initiated by signals from both outside and inside the cell. Extrinsic triggers come from death receptors on the cell surface binding ligands from other cells, which begins a cascade that activates initiator caspases and then the executioner caspases. Intrinsic triggers arise from within the cell due to stress such as DNA damage, oxidative stress, or ER stress; these signals cause mitochondria to release cytochrome c, form the apoptosome, activate caspase-9, and then activate downstream caspases. These two pathways converge on the common caspase execution program, and there can even be cross-talk between them.

So, the idea that only extracellular signals initiate apoptosis isn’t accurate, because intracellular stress signals can also start the process. Saying apoptosis is independent of signaling would also be incorrect, since it is driven by regulated signaling cascades.