Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface

By G. Csordás, P. Várnai, Tünde Golenár, Swati Roy, George Purkins, T. Schneider, T. Balla, G. Hajnóczky. Molecules and Cells, 2010

727 citations recorded by the source corpus.

The ER-mitochondrial junction provides a local calcium signaling domain that is critical for both matching energy production with demand and the control of apoptosis. Here, we visualize ER-mitochondrial contact sites and monitor the localized [Ca2+] changes ([Ca2+]ER-mt) using drug-inducible fluorescent interorganelle linkers. We show that all mitochondria have contacts with the ER but plasma membrane-mitochondrial contacts are less frequent because of interleaving ER stacks in both RBL-2H3 and H9c2 cells. Single mitochondria display discrete patches of ER contacts and show heterogeneity in the ER-mitochondrial Ca2+ transfer. Pericam-tagged linkers revealed IP3-induced [Ca2+]ER-mt signals that exceeded 9μM and endured buffering bulk cytoplasmic [Ca2+] increases. Altering linker length to modify the space available for the Ca2+ transfer machinery had a biphasic effect on [Ca2+]ER-mt signals. These studies provide direct evidence for the existence of high Ca2+ microdomains between the ER and mitochondria, and suggest an optimal gap width for efficient Ca2+ transfer.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bb61887f5d915a6d8e9b044f502f6ca05173c6a2

Citations in the corpus

• Upregulated function of mitochondria-associated ER membranes in Alzheimer disease (2012, unknown): “…to mitochondria that is involved in a number of key metabolic functions (Hayashi et al , 2009), including cholesterol metabolism (Rusinol et al , 1994), the synthesis and transfer of phospholipids between the ER and mitochondria (Vance, 2003), and calcium homeostasis (Csordas et al , 2010).”