Mitochondria: From physiology to pathology

Over the past decade, the role of mitochondria has extended beyond those tasks for which these organelles are historically known. Recent proteomics investigations have highlighted the extraordinary complexity of mitochondrial protein organization, which is a reflection of the numerous and disparate mitochondrial functions. These include the synthesis of most of the ATP present in the cell, apoptosis, ion homeostasis, cellular stress response, antioxidant control, redox regulation, mitophagy, involvement in various biosynthetic pathways and many more processes. Furthermore, mitochondria are dynamic organelles, and their morphology can vary significantly within a cell. This is mainly due to the mitochondrial fusion and fission processes, referred as mitochondrial dynamics, which are crucial for the organelles’ interactions with other cell compartments and for the cross-talk with the cell cycle and metabolism as well as differentiation and senescence. An intriguing feature of mitochondria is that they possess their own DNA (mtDNA), which is functionally coordinated with the nuclear genome. Indeed, numerous nucleus-encoded proteins are required for complex molecular processes such as replication, transcription, RNA processing and degradation, translation, and assembly of respiratory chain complexes that take place inside the mitochondria. On the other hand, mitochondrial gene expression plays an important role in the communication between mitochondria and the nucleus, contributing to the regulation of cell physiology. Recent studies have pointed to novel RNA-driven mechanisms according to which mitochondrial-derived transcripts, in addition to their role in maintaining mitochondrial function, act as signalling molecules modulating the innate immune response.