Pierre-Jean Desmaison, Giulia Bertolin
Mitochondria are traditionally viewed as a homogeneous network supporting cellular energy production. However, increasing evidence reveals substantial heterogeneity across biological scales, from intramitochondrial microdomains to specialised mitochondrial populations within cells and tissues. These subpopulations differ in morphology, metabolism, bioenergetics, and spatial organisation, reflecting adaptation to local functional demands. In this Review, we discuss the mechanisms underlying mitochondrial heterogeneity, the emerging concept of mitochondrial subclasses, their functional integration within cellular metabolism, and the challenge of distinguishing stable subclasses from transient states. We propose a shift from a network-based view toward a dynamic mitochondrial ecosystem with important implications for physiology and disease.