[HTML][HTML] Ca2+ transfer from the ER to mitochondria: when, how and why

R Rizzuto, S Marchi, M Bonora, P Aguiari… - … et Biophysica Acta (BBA …, 2009 - Elsevier
Biochimica et Biophysica Acta (BBA)-Bioenergetics, 2009Elsevier
The heterogenous subcellular distribution of a wide array of channels, pumps and
exchangers allows extracellular stimuli to induce increases in cytoplasmic Ca2+
concentration ([Ca2+] c) with highly defined spatial and temporal patterns, that in turn induce
specific cellular responses (eg 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 …
The heterogenous subcellular distribution of a wide array of channels, pumps and exchangers allows extracellular stimuli to induce increases in cytoplasmic Ca2+ concentration ([Ca2+]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 [Ca2+] in the mitochondrial matrix ([Ca2+]m) invariably follow the cytosolic rises. Given the low affinity of the mitochondrial Ca2+ transporters, the close proximity to the endoplasmic reticulum (ER) Ca2+-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 Ca2+ 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 [Ca2+]m increases, and iv) the effects of oncogene-mediated signals on mitochondrial Ca2+ homeostasis. Despite the rapid progress carried out in the latest years, a deeper molecular understanding is still needed to unlock the secrets of Ca2+ signaling machinery.
Elsevier