• Mitochondria are cellular organelles that play a crucial role in energy metabolism and also participate in cell signaling. Mitochondria can release various signaling molecules, such as reactive oxygen species (ROS), mitochondrial DNA, mitochondrial transcription factors, and metabolites, which can be transmitted into the cytoplasm and the cell nucleus, influencing diverse processes such as gene expression, cell cycle, and apoptosis. Herein, we propose the concept and framework of Mitochondrial Signal Communication (MSC) to systematically decipher and understand the signaling communication of mitochondria. Furthermore, we construct the MitoCommun database, including 580 mitochondrial signal entries in Homo sapiens, Mus musculus, Rattus norvegicus, and Caenorhabditis elegans, to offer user-friendly browsing and searching functions to support various mitochondria-based applications.