Stromal Interaction Molecule 1 (STIM1) Is Involved in the Regulation of Mitochondrial Shape and Bioenergetics and Plays a Role in Oxidative Stress

Henke, Nadine; Albrecht, Philipp; Pfeiffer, Annika; Toutzaris, Diamandis; Zanger, Klaus; Methner, Axel

doi:10.1074/jbc.m112.417212

Cited by 59 publications

(45 citation statements)

References 37 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in STIM1 null cells they found that normal mitochondrial structure was disrupted and metabolic rate increased. It has also been shown that STIM1 is s-glutathionylated in response to oxidative stress, resulting in increased SOCE and altered mitochondrial Ca 2ϩ homeostasis (29); however, contrary to the work of Henke et al (30) they found that a reduction in STIM1/Orai1 is protective in terms of oxidative stress. These studies provide evidence that STIM1 contributes to the regulation of both mitochondrial homeostasis and oxidative stress.…”

Section: Potential Role For Stim1-mediated Soce In Ischemia/reperfusicontrasting

confidence: 53%

“…In addition, the ER stress protein ERp57 has been shown to interact with STIM1 and modulate SOCE (94). Henke et al (30) also found that in STIM1-deficient cells there was increased phosphorylation of EReIF2␣ and PERK, further supporting a role for STIM1 in mediating ER stress response.…”

Section: Orai1/trpcmentioning

confidence: 80%

“…Recently, Henke et al (30) reported that STIM1 and Orai1 knockdown increased sensitivity of cells to oxidative stress and that the converse was also true. Moreover, in STIM1 null cells they found that normal mitochondrial structure was disrupted and metabolic rate increased.…”

Section: Potential Role For Stim1-mediated Soce In Ischemia/reperfusimentioning

confidence: 99%

See 2 more Smart Citations

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

Collins

Zhu-Mauldin

Marchase

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

110

102

View full text Add to dashboard Cite

Collins HE, Zhu-Mauldin X, Marchase RB, Chatham JC. STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology. Am J Physiol Heart Circ Physiol 305: H446 -H458, 2013. First published June 21, 2013 doi:10.1152/ajpheart.00104.2013.-Store-operated Ca 2ϩ entry (SOCE) is critical for Ca 2ϩ signaling in nonexcitable cells; however, its role in the regulation of cardiomyocyte Ca 2ϩ homeostasis has only recently been investigated. The increased understanding of the role of stromal interaction molecule 1 (STIM1) in regulating SOCE combined with recent studies demonstrating the presence of STIM1 in cardiomyocytes provides support that this pathway co-exists in the heart with the more widely recognized Ca 2ϩ handling pathways associated with excitation-contraction coupling. There is now substantial evidence that STIM1-mediated SOCE plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo, and there is growing support for the contribution of SOCE to Ca 2ϩ overload associated with ischemia/reperfusion injury. Here, we provide an overview of our current understanding of the molecular regulation of SOCE and discuss the evidence supporting the role of STIM1/Orai1-mediated SOCE in regulating cardiomyocyte function.store-operated Ca 2ϩ entry; stromal interaction molecule 1; orai1; cardiomyocytes STORE-OPERATED CA 2ϩ ENTRY (SOCE), also known as capacitative calcium entry (CCE), is the major mechanism of Ca 2ϩ entry in nearly all nonexcitable cells (97, 99). In addition, it is increasingly recognized to co-exist with voltage-gated Ca 2ϩ channels in excitable cells, including neurons, skeletal muscle cells, and cardiomyocytes (1,38,45,83,121). In response to inositol 1,4,5-triphosphate (IP 3 )-(43) or ryanodine receptor (RyR)-mediated (3) Ca 2ϩ release from ER/SR stores, SOCE facilitates the influx of Ca 2ϩ from the extracellular space, resulting in a sustained increase in cytosolic Ca 2ϩ levels. Thus, although one of the roles of SOCE is to rapidly refill the depleted ER/SR stores, the subsequent sustained increase in cytosolic Ca 2ϩ also regulates numerous gene transcription pathways (33,50,151). Indeed, aberrant SOCE has been observed in a growing number of diseases including severe combined immunodeficiency, acute pancreatitis, and Alzheimer's disease (86).The integration of SOCE into well-established models of Ca 2ϩ homeostasis was hampered for many years by the lack of specific molecular mediators; even as recently as 2004 there was considerable controversy as to the specific mechanisms regulating SOCE (90, 113). However, in 2005, stromal interaction molecule 1 (STIM1) was found to localize to the ER/SR membrane and shown to function as a primary mediator of SOCE (54, 102). The putative physiological and pathophysiological roles of SOCE and STIM1 that have been identified to date are summarized in Table 1. A number of studies have recently reported the presence of STIM1 in adult cardiomyocytes (37,59,153), and consistent with earlier evidence supporting a rol...

show abstract

Section: Potential Role For Stim1-mediated Soce In Ischemia/reperfusicontrasting

confidence: 53%

Section: Orai1/trpcmentioning

confidence: 80%

See 1 more Smart Citation

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

Collins

Zhu-Mauldin

Marchase

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

110

102

View full text Add to dashboard Cite

show abstract

“…SOCE was quantified by a highthroughput method previously validated using STIM1 − / − mouse embryonic fibroblasts and shown to be reliable. 40 Ratiometric Fura2-AM values were converted to absolute Ca 2+ values as described 41 and analyzed with Attovision (BD Bioscience). For measuring the Ca 2+ kinetics of B and T cells, splenocytes were incubated with 3 μM Fluo8 for 30 min at RT.…”

Section: Ca 2+ Measurementsmentioning

confidence: 99%

BAX inhibitor-1 is a Ca2+ channel critically important for immune cell function and survival

et al. 2015

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) serves as the major intracellular Ca 2+ store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca 2+ leak channel also implicated in the response against protein misfolding, thereby connecting the Ca 2+ store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca 2+ levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca 2+ levels, suggesting an exhausted mitochondrial Ca 2+ buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca 2+ homeostasis in lymphocytes. Cell Death and Differentiation (2016) 23, 358-368; doi:10.1038/cdd.2015; published online 16 October 2015The endoplasmic reticulum (ER) serves as the major intracellular calcium (Ca 2+ ) store, the release of which controls a vast array of cellular functions from short-term responses such as contraction and secretion to long-term regulation of cell growth and proliferation. 1 Dysregulated release of ER Ca 2+ , in contrast, initiates programmed cell death by several mechanisms including mitochondrial Ca 2+ overload, depolarization, ATP loss and cytochrome c release. 2 Besides this, the ER also has a key role in the synthesis, folding and sorting of proteins destined for the secretory pathway. The deleterious consequences of an increase in unfolded proteins is called ER stress and can be antagonized by the unfolded protein response (UPR), a mechanism that coordinates a simultaneous increase in the ER folding capacity and a decrease in folding load. In the case of insufficient adaptation to ER stress, cells undergo apoptosis. 3 BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is an evolutionarily conserved protein that bridges both the Ca 2+ homeostasis and UPR functions of the ER. 4 BI-1 was first identified in a screen for human proteins capable of inhibiting BAX-mediated cell death in yeast. 5 In mammalian cells, BI-1's antiapoptotic function is most pronounced in paradigms of ER stress 6 and involves changes in the amount of Ca 2+ that can be released from intracellular stores. 6,7 BI-1 is a highly hydrophobic protein that forms a Ca 2+ pore responsible for its Ca 2+ leak properties 8 and is the founding member of a family of six proteins with similar properties. 9 The increase in the ER Ca 2+ lea...

show abstract

“…STIM1 is a transmembrane ER protein containing multiple functional domains, and it serves as an ER Ca 2ϩ sensor and activator of store-operated Ca 2ϩ entry (SOCE) (44 -46). Studies have shown that Stim1 is associated with oxidative stress and mitochondrial bioenergetics (47). We found that suppression of Stim1 in Sertoli cells in the cultured testis in vitro increased ROS production and caused a global disruption of gonads, evidenced by disorganized testicular cord formation, obstruction of angiogenesis, and loss of interstitium.…”

Section: Discussionmentioning

confidence: 72%

Quantitative Proteomics Reveals the Essential Roles of Stromal Interaction Molecule 1 (STIM1) in the Testicular Cord Formation in Mouse Testis

Zheng

Zhao

Zhang

et al. 2015

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Testicular cord formation in male gonadogenesis involves assembly of several cell types, the precise molecular mechanism is still not well known. With the high-throughput quantitative proteomics technology, a comparative proteomic profile of mouse embryonic male gonads were analyzed at three time points (11.5, 12.5, and 13.5 days post coitum), corresponding to critical stages of testicular cord formation in gonadal development. 4070 proteins were identified, and 338 were differentially expressed, of which the Sertoli cell specific genes were significant enrichment, with mainly increased expression across testis cord development. Additionally, we found overrepresentation of proteins related to oxidative stress in these Sertoli cell specific genes. Of these differentially expressed oxidative stress-associated Sertoli cell specific protein, stromal interaction molecule 1, was found to have discrepant mRNA and protein regulations, with increased protein expression but decreased mRNA levels during testis cord development. Knockdown of Stim1 in Sertoli cells caused extensive defects in gonadal development, including testicular cord disruption, loss of interstitium, and failed angiogenesis, together with increased levels of reactive oxygen species. And suppressing the aberrant elevation of reactive oxygen species could partly rescue the defects of testicular cord development. Taken together, our results suggest that reactive oxygen species regulation in Sertoli cells is important for gonadogenesis, and the quantitative proteomic data could be a rich resource to the elucidation of regulation of testicular cord development. Molecular & Cellular

show abstract

Stromal Interaction Molecule 1 (STIM1) Is Involved in the Regulation of Mitochondrial Shape and Bioenergetics and Plays a Role in Oxidative Stress

Cited by 59 publications

References 37 publications

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

BAX inhibitor-1 is a Ca2+ channel critically important for immune cell function and survival

Quantitative Proteomics Reveals the Essential Roles of Stromal Interaction Molecule 1 (STIM1) in the Testicular Cord Formation in Mouse Testis

Contact Info

Product

Resources

About