title: Ca(2+) transfer from the ER to mitochondria: when, how and why.
abstract: The heterogenous subcellular distribution of a wide array of channels, pumps and exchangers allows extracellular stimuli to induce increases in cytoplasmic Ca(2+) concentration ([Ca(2+)]c) with highly defined spatial and temporal patterns, that in turn induce specific cellular responses (e.g. contraction, secretion, proliferation or cell death). In this extreme complexity, the role of mitochondria was considered marginal, till the direct measurement with targeted indicators allowed to appreciate that rapid and large increases of the [Ca(2+)] in the mitochondrial matrix ([Ca(2+)]m) invariably follow the cytosolic rises. Given the low affinity of the mitochondrial Ca(2+) transporters, the close proximity to the endoplasmic reticulum (ER) Ca(2+)-releasing channels was shown to be responsible for the prompt responsiveness of mitochondria. In this review, we will summarize the current knowledge of: i) the mitochondrial and ER Ca(2+) channels mediating the ion transfer, ii) the structural and molecular foundations of the signaling contacts between the two organelles, iii) the functional consequences of the [Ca(2+)]m increases, and iv) the effects of oncogene-mediated signals on mitochondrial Ca(2+) homeostasis. Despite the rapid progress carried out in the latest years, a deeper molecular understanding is still needed to unlock the secrets of Ca(2+) signaling machinery.
authors.affiliation: Dept. Biomedical Sciences, University of Padua, Via Colombo 3, Padua 35121, Italy. rosario.rizzuto@unipd.it
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Saverio
authors.initials: S
authors.lastname: Marchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.forename: Paola
authors.initials: P
authors.lastname: Aguiari
authors.forename: Angela
authors.initials: A
authors.lastname: Bononi
authors.forename: Diego
authors.initials: D
authors.lastname: De Stefani
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giorgi
authors.forename: Sara
authors.initials: S
authors.lastname: Leo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rimessi
authors.forename: Roberta
authors.initials: R
authors.lastname: Siviero
authors.forename: Erika
authors.initials: E
authors.lastname: Zecchini
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton