Perturbed mitochondrial Ca 2+ 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 (Ca 2+) uptake. Rapid Ca 2+ 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 Ca 2+ stores. In mitophagy, the role of Ca 2+ remains obscure. What role does mitochondrial Ca 2+ play in metabolic sensing or in mitochondrial remodeling? Is endoplasmic reticulum (ER)-Ca 2+ crosstalk involved? These are some of the questions that we address in this review.