Mitochondrial metabolism as a regulator of keratinocyte differentiation

Mitochondrial metabolism has traditionally been thought of as a source of cellular energy in the form of ATP. The recent renaissance in the study of cellular metabolism, particularly in the cancer field, has highlighted the fact that mitochondria are also critical biosynthetic and signaling hubs, making these organelles key governors of cellular outcomes.^1-5 Using the epidermis as a model system, our recent study looked into the role that mitochondrial metabolism and ROS production play in cellular differentiation in vivo.⁶ We showed that conditional deletion of the mitochondrial transcription factor, TFAM within the basal cells of the epidermis results in loss of mitochondrial ROS production and impairs epidermal differentiation and hair growth. We demonstrated that mitochondrial ROS generation is required for the propagation of Notch and β-catenin signals which promote epidermal differentiation and hair follicle development respectively. This study bolsters accumulating evidence that oxidative mitochondrial metabolism plays a causal role in cellular differentiation programs. It also provides insights into the role that mitochondrial oxidative signaling plays in a cell type-dependent manner.