Perturbed mitochondrial Ca2+ signals as causes or consequences of mitophagy induction

Mitophagy is an essential process that maintains mitochondrial quality and number, thus limiting cellular degeneration. Along with apoptosis, mitophagy participates in cellular fate decisions by eliminating damaged mitochondria. A variety of mitochondrial parameters, such as structure, membrane potential and reactive oxygen species, are key determinants in triggering the mitophagic machinery. These parameters are also important regulators of the mitochondrial capacity for calcium (Ca2+) uptake. Rapid Ca2+ accumulation in the mitochondrial matrix allows for prompt stimulation of the organelle. This process requires a close morphofunctional coupling between mitochondria and the main intracellular Ca2+ stores. In mitophagy, the role of Ca2+ remains obscure. What role does mitochondrial Ca2+ play in metabolic sensing or in mitochondrial remodeling? Is endoplasmic reticulum (ER)-Ca2+ crosstalk involved? These are some of the questions that we address in this review.