Mitochondrial compartments (OMM, IMS, IMM, and matrix) maintain organelle function and homeostasis while harboring the potential to enable, initiate, and execute apoptosis. A brief summary of each mitochondrial compartment’s activities and/or signaling pathways that directly communicate to the apoptosis machinery are indicated. Detailed descriptions are provided in the text. Abbreviations: AIF, apoptosis-inducing factor; cyt c, cytochrome c; ETC, electron transport chain; ROS, reactive oxygen species; TCA, tricarboxylic acid; VDAC, voltage-dependent anion channel.