Calcium Regulates the Association between Mitochondria and a Smooth Subdomain of the Endoplasmic Reticulum

Abstract

Association between the ER and mitochondria has long been observed, and the formation of close contacts between ER and mitochondria is necessary for the ER-mediated sequestration of cytosolic calcium by mitochondria. Autocrine motility factor receptor (AMF-R) is a marker for a smooth subdomain of the ER, shown here by confocal microscopy to be distinct from, yet closely associated with the calnexin- or calreticulin-labeled ER. By EM, smooth ER AMF-R tubules exhibit direct interactions with mitochondria, identifying them as a mitochondria-associated smooth ER subdomain. In digitonin-permeabilized MDCK cells, the addition of rat liver cytosol stimulates the dissociation of smooth ER and mitochondria under conditions of low calcium. Using BAPTA chelators of various affinities and CaEGTA buffers of defined free Ca2+ concentrations and quantitative confocal microscopy, we show that free calcium concentrations <100 nM favor dissociation, whereas those >1 μM favor close association between these two organelles. Therefore, we describe a cellular mechanism that facilitates the close association of this smooth ER subdomain and mitochondria when cytosolic free calcium rises above physiological levels.

Autocrine motility factor/phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release

“…AMF/PGI affect on [Ca 2 þ ] cyt elevation was not however affected by mitochondrial uncoupling, suggesting that it is not related to mitochondrial association of the gp78/AMFRlabeled smooth ER domain. 24,32 It was also not associated with changes in ER Ca 2 þ content. AMF/PGI interaction with gp78/AMFR, therefore, regulates ER Ca 2 þ release upon ER stress.…”

“…11 The gp78/AMFRpositive smooth ER domain is closely associated with mitochondria and this interaction is regulated by [Ca 2 þ ] cyt . 24,32 In response to TG and TUN, AMF/PGI reduced the peak amplitude although not total (AUC) elevation of [Ca 2 þ ] cyt and importantly affected the rate of Ca 2 þ uptake to mitochondria. AMF/PGI affect on [Ca 2 þ ] cyt elevation was not however affected by mitochondrial uncoupling, suggesting that it is not related to mitochondrial association of the gp78/AMFRlabeled smooth ER domain.…”

Gangliosides as apoptotic signals in ER stress response

“…Ca 2 þ also regulates the association between mitochondria and a smooth domain of the ER and enhances the ability of gangliosides to produce membrane clusters. 89 Whether mitochondrial damage occurs through ganglioside interaction with a candidate component of the PTP or through direct perturbation of mitochondrial membranes and, in turn, PTP function, remains to be elucidated. However, the fact that GD3-mediated opening of PTPs is antagonized by known PT inhibitors (e.g., cyclosporin A, ADP, trifluoperazine, and Mg 2 þ ) suggests that GD3 acts directly at the pore level.…”

Microdomains for Dopamine Volume Neurotransmission in Primate Prefrontal Cortex

“…What is very interesting, however, is that both the SSC and mitochondria are most certainly dynamic structures, unlike their static images captured in electron microscopy. Early ultrastructural studies have demonstrated that SSCs are capable of plastic changes after axotomy and during development (Sumner, 1975;Buschmann, 1979), and recent evidence indicates that local Ca 2ϩ dynamics may affect physical coupling between the smooth endoplasmic reticulum and mitochondria (Wang et al, 2000). Finally, we should consider the possibility of a dynamic trafficking between the plasmalemmal component and the cytoplasmic pool of the D 5 R, as might indicate its selective clustering bellow the microdomain, often in association with clathrincoated vesicles (Fig.…”