The yin and yang of mitochondrial Ca2+ signaling in cell physiology and pathology

Mitochondria are autonomous and dynamic cellular organelles orchestrating a diverse range of cellular activities. Numerous cell-signaling pathways target these organelles and Ca is one of the most significant. Mitochondria are able to rapidly and transiently take up Ca, thanks to the mitochondrial Ca uniporter complex, as well as to extrude it through the Na/Ca and H/Ca exchangers. The transient accumulation of Ca in the mitochondrial matrix impacts on mitochondrial functions and cell pathophysiology. Here we summarize the role of mitochondrial Ca signaling in both physiological (yang) and pathological (yin) processes and the methods that can be used to investigate mitochondrial Ca homeostasis. As an example of the pivotal role of mitochondria in pathology, we described the state of the art of mitochondrial Ca alterations in different pathological conditions, with a special focus on Alzheimer's disease.