We report Ca²⁺-induced release of Ca²⁺ from mitochondria (mCICR) dependent on transitory opening of the permeability transition pore (PTP) operating in a low conductance mode. The Ca²⁺ fluxes taking place during mCICR are a direct consequence of the mitochondrial depolarization spike (mDPS) caused by PTP opening. Both mDPS and mCICR can propagate from one mitochondrion to another in vitro, generating traveling depolarization and Ca²⁺ waves. Mitochondria thus appear to be excitable organelles capable of generating and conveying electrical and Ca²⁺ signals. In living cells, mDPS/mCICR is triggered during IP₃- induced Ca²⁺ mobilization and results in the amplification of the Ca²⁺ signals primarily emitted from the endoplasmic reticulum.