Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Nov;1787(11):1342-51.
doi: 10.1016/j.bbabio.2009.03.015. Epub 2009 Mar 31.

Ca(2+) transfer from the ER to mitochondria: when, how and why

Rosario Rizzuto  1 , Saverio Marchi, Massimo Bonora, Paola Aguiari, Angela Bononi, Diego De Stefani, Carlotta Giorgi, Sara Leo, Alessandro Rimessi, Roberta Siviero, Erika Zecchini, Paolo Pinton
Affiliations
Review

Ca(2+) transfer from the ER to mitochondria: when, how and why

Rosario Rizzuto et al. Biochim Biophys Acta. 2009 Nov.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Schematical representation of mitochondria-ER contact sites and Ca2+ handling. Agonist stimulation induces IP3 synthesis and consequently opening of IP3R channel, which causes Ca2+ redistribution. SERCA, sercoplasmic/endoplasmic calcium ATPase; VDAC, voltage dependent anion channel; MCU, mitochondrial calcium uniporter; IP3R, IP3 receptor; (B) Combined 3D imaging of mitochondria and ER in a HeLa cell transiently expressing mtBFP(Y66H, Y145F) and erGFP(S65T) (5). (C) Rappresentative traces of ER and mitochondrial calcium response during agonist stimulation measured using specifically trageted aequorins.
Figure 2
Figure 2
Anti-apoptotic proteins Bcl-2 and Akt affect ER calcium homeostasis by differential mechanisms. (A) Bcl-2 overexpression increases the Ca2+ leak, while leaving Ca2+ accumulation unaffected, hence reducing the steady-state [Ca2+] levels. (B) Akt hyper-activation induces a decrease in ER Ca2+ release, probably through phosphorylation of IP3R. As a direct consequence, the [Ca2+] increases caused by IP3-generating agonists were reduced in amplitude in both cytosol and mitochondria. Kinetics and [Ca2+] during agonist stimulation measured by ER targeted aequorin in Bcl-2 overexpression or AKT hyper-activation conditions, are shown in the respective panels.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hajnoczky G, Csordas G, Madesh M, Pacher P. The machinery of local Ca2+ signalling between sarco-endoplasmic reticulum and mitochondria. J Physiol. 2000;529(Pt 1):69–81. - PMC - PubMed
    1. Hajnoczky G, Csordas G, Yi M. Old players in a new role: mitochondria-associated membranes, VDAC, and ryanodine receptors as contributors to calcium signal propagation from endoplasmic reticulum to the mitochondria. Cell calcium. 2002;32:363–377. - PubMed
    1. Mao C, Kim SH, Almenoff JS, Rudner XL, Kearney DM, Kindman LA. Molecular cloning and characterization of SCaMPER, a sphingolipid Ca2+ release-mediating protein from endoplasmic reticulum. Proc Natl Acad Sci U S A. 1996;93:1993–1996. - PMC - PubMed
    1. Galione A, Churchill GC. Interactions between calcium release pathways: multiple messengers and multiple stores. Cell calcium. 2002;32:343–354. - PubMed
    1. Oh-hora M, Rao A. Calcium signaling in lymphocytes. Curr Opin Immunol. 2008;20:250–258. - PMC - PubMed

Publication types

MeSH terms

Substances