Mithocondrial physiology and calcium signalling partnership: from regulation of differentiation to oncosuppressor activity

In recent years, mitochondria have gained much interest as organelles involved not only in the processes of obtaining energy, but also associated with novel roles in cell physiopathology. These roles range from mitochondria being the site for lipid synthesis, through constituting a buffering system for intracellular calcium, and from being a mediator of reactive oxygen species signalling to a regulator of different cell death types. This group of roles requires a highly regulated system of signalling mechanisms. One of these emerging mechanisms is the communication between the mitochondria and the endoplasmic reticulum. In fact, mitochondria and endoplasmic reticulum are tightly associated, in a region called mitochondria associated membranes, where several signalling events allow continuous communication between the two organelles. Among these signalling events, calcium signalling has been considered of great importance. Advanced techniques of molecular biology allow the development of tools for the investigation of these complex subcellular compartments. Particularly useful are those based on the green fluorescent protein and the calcium sensitive luminescent protein, aequorin. In this work, the aforementioned tools have been used to investigate mitochondrial physiology, especially its communications with the endoplasmic reticulum. Two different cellular events were studied: i) the regulation of apoptosis by a strategic oncosuppressor, p53 and ii) differentiation of oligodendrocytes progenitor cells into adult oligodendrocytes during stress condition generated by cytokines. Performed experiments allowed the describing of the endoplasmic reticulum as a new intracellular localization site of p53, where it increases the luminal calcium concentration, promoting the sensitivity to calcium dependent apoptotic stimuli. Simultaneously, it has been revealed how mitochondria are a target for TNFα in oligodendrocytes progenitors, where it promotes reactive oxygen species production and impairment of the respiratory chain activity, inhibiting cell differentiation without promoting cell death. In conclusion, these approaches reveal completely new relations between mitochondria, calcium signalling and cell physiology, shedding new light on the role for this fascinating organelle