Mitochondrial quality control and the microphthalmia/transcription factor E (MiTF/TFE) family

Mitochondria quality control involves the synchronization of several mechanisms that guarantee the regulation and maintenance of mitochondrial homeostasis. Among them, the selective degradation of mitochondria through mitophagy and the biogenesis of new mitochondria are two crucial processes whose modulation may rely on the crosstalk between mitochondria and lysosomes. The signaling cascades that link the functions of these organelles are highly entrusted to the activity of AMPK, a major intracellular signaling hub able to regulate cell metabolism. The role of this hub is essential for perceiving signals related to mitochondrial activity and integrating them toward other cell compartments, including lysosomes. The targets of AMPK include the MITF/TFE transcription factors, in particular, TFEB, which is considered the master regulator of autophagy and lysosomal functions but has also been associated with the induction of mitophagy and mitochondrial biogenesis. Overall, the AMPK-TFEB signaling pathway allows the coordination of mitochondrial and lysosomal activities, ensuring the functional communication between these cell compartments and participating in the regulation of the dynamics of both organelles.