Endoplasmic Reticulum/Mitochondria Calcium Cross‐Talk

Romagnoli, Anna; Aguiari, Paola; Stefani, Diego De; Leo, Sara; Marchi, Saverio; Rimessi, Alessandro; Zecchini, Erika; Pinton, Paolo; Rizzuto, Rosario

doi:10.1002/9780470725207.ch9

Cited by 25 publications

(21 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The C-terminal region containing a lysine-rich motif (EKDKKKEKK) has been identified as a pH sensor of the BI-1 Ca 2ϩ channel (7), being essential for tetramerization and the Ca 2ϩ -release properties of BI-1. Given the central role of the ER in controlling cell-survival and cell-death responses (17)(18)(19)(20)(21)(22)(23), it is reasonable to assume that the activity of BI-1 as a Ca 2ϩ channel can be an important determinant in these processes. However, the exact topology of BI-1 in the ER membrane and the position of the Ca 2ϩ pore are still unresolved.…”

Section: The Endoplasmic Reticulum (Er)mentioning

confidence: 99%

The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore

Bultynck

Kiviluoto

Henke

et al. 2012

Journal of Biological Chemistry

102

View full text Add to dashboard Cite

Background: Evolutionary conserved Bax inhibitor-1 (BI-1) protects against ER stress-mediated apoptosis. Results: We identified a Ca 2ϩ -permeable channel pore in the C terminus of BI-1. Critical pore properties are an ␣-helical structure and two aspartate residues conserved among animals, but not among plants and yeast. Conclusion: C-terminal domain of BI-1 harbors a Ca 2ϩ -permeable channel pore. Significance: BI-1 has Ca 2ϩ channel properties likely relevant for its function in ER stress and apoptosis. Bax inhibitor-1 (BI-1) is a multitransmembrane domainspanning endoplasmic reticulum (ER)-located protein that is evolutionarily conserved and protects against apoptosis and ER stress. Furthermore, BI-1 is proposed to modulate ER Ca 2؉homeostasis by acting as a Ca 2؉ -leak channel. Based on experimental determination of the BI-1 topology, we propose that its C terminus forms a Ca 2؉ pore responsible for its Ca 2؉ -leak properties. We utilized a set of C-terminal peptides to screen for Ca 2؉ leak activity in unidirectional 45 Ca 2؉ -flux experiments and identified an ␣-helical 20-amino acid peptide causing Ca 2؉ leak from the ER. The Ca 2؉ leak was independent of endogenous ER Ca 2؉ -release channels or other Ca 2؉ -leak mechanisms, namely translocons and presenilins. The Ca 2؉ -permeating property of the peptide was confirmed in lipid-bilayer experiments. Using mutant peptides, we identified critical residues responsible for the Ca 2؉ -leak properties of this BI-1 peptide, including a series of critical negatively charged aspartate residues. Using peptides corresponding to the equivalent BI-1 domain from various organisms, we found that the Ca 2؉ -leak properties were conserved among animal, but not plant and yeast orthologs. By mutating one of the critical aspartate residues in the proposed Ca 2؉ -channel pore in full-length BI-1, we found that Asp-213 was essential for BI-1-dependent ER Ca 2؉ leak. Thus, we elucidated residues critically important for BI-1-mediated Ca 2؉ leak and its potential channel pore. Remarkably, one of these residues was not conserved among plant and yeast BI-1 orthologs, indicating that the ER Ca2؉ -leak properties of BI-1 are an added function during evolution. leak from the ER (9, 10). BI-1 seems to be strongly evolutionarily conserved and BI-1 orthologs from plants can substitute for mammalian BI-1 in regard to its anti-apoptotic function (11). Besides this, other diverse functions of BI-1 have been described. BI-1 is a negative regulator of the ER-stress sensor (12), it interacts with G-actin and increases actin polymerization (13), enhances cancer metastasis by altering glucose metabolism and by activating a sodium-hydrogen exchanger (14), and it reduces production of reactive oxygen species through direct interaction with NADPH-P450 reductase (15), a member of the microsomal monooxygenase system.Recently, the role of BI-1 in Ca 2ϩ signaling has been further explored. The effect of BI-1 on cell death seems to involve changes in the amount of Ca 2ϩ that is releasable from intrace...

show abstract

Section: The Endoplasmic Reticulum (Er)mentioning

confidence: 99%

The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore

Bultynck

Kiviluoto

Henke

et al. 2012

Journal of Biological Chemistry

102

View full text Add to dashboard Cite

show abstract

“…Mitochondria are deeply integrated in cell biology, with roles in urea, porphyrin [5] and steroid hormone synthesis [6], apoptosis [7], calcium homeostasis [8] and free radical production [9,10 ]. Changes in mitochondrial shape by active fusion and fission are vital for cell function [11 ].…”

Section: Mitochondrial Genetics and Biologymentioning

confidence: 99%

Disorders of mitochondrial function

Debray

Lambert

Mitchell

2008

Current Opinion in Pediatrics

View full text Add to dashboard Cite

“…In human ASM, mitochondria are present in large numbers (79), and, interestingly, mitochondrial biogenesis is enhanced in asthma (28). Whether such changes can contribute to altered Ca 2ϩ homeostasis or other features of asthma, such as airway remodeling, is not known.Mitochondrial Ca 2ϩ uptake during agonist stimulation has been observed in different cell types (13,25,33,38,48,55,56,65) and is thought to decrease local Ca 2ϩ gradients for sarcoplasmic reticulum (SR)/endoplasmic reticulum Ca 2ϩ refilling while maintaining or enhancing store-operated Ca 2ϩ entry (SOCE) (24,37,41,45,50,81). Some theoretical models of Ca 2ϩ signaling in smooth muscle that include mitochondria also suggest a role for modulating [Ca 2ϩ ] cyt regulatory mechanisms (66, 67).…”

mentioning

confidence: 99%

“…These studies raise the question of the relation between the spatial localization of mitochondria and their ability to buffer or release Ca 2ϩ . Recent work has established that mitochondria contain sophisticated Ca 2ϩ uptake and release mechanisms that may alter [Ca 2ϩ ] cyt either globally or in the vicinity of the SR and PM (10,13,16,22,25,33,38,43,48,52,60,62,63,65,70). There is currently little information on these roles for mitochondria in ASM cells.…”

mentioning

confidence: 99%

Inflammation alters regional mitochondrial Ca²⁺ in human airway smooth muscle cells

Delmotte

Yang

Thompson

et al. 2012

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Regulation of cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in airway smooth muscle (ASM) is a key aspect of airway contractility and can be modulated by inflammation. Mitochondria have tremendous potential for buffering [Ca(2+)](cyt), helping prevent Ca(2+) overload, and modulating other intracellular events. Here, compartmentalization of mitochondria to different cellular regions may subserve different roles. In the present study, we examined the role of Ca(2+) buffering by mitochondria and mitochondrial Ca(2+) transport mechanisms in the regulation of [Ca(2+)](cyt) in enzymatically dissociated human ASM cells upon exposure to the proinflammatory cytokines TNF-α and IL-13. Cells were loaded simultaneously with fluo-3 AM and rhod-2 AM, and [Ca(2+)](cyt) and mitochondrial Ca(2+) concentration ([Ca(2+)](mito)) were measured, respectively, using real-time two-color fluorescence microscopy in both the perinuclear and distal, perimembranous regions of cells. Histamine induced a rapid increase in both [Ca(2+)](cyt) and [Ca(2+)](mito), with a significant delay in the mitochondrial response. Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger (1 μM CGP-37157) increased [Ca(2+)](mito) responses in perinuclear mitochondria but not distal mitochondria. Inhibition of the mitochondrial uniporter (1 μM Ru360) decreased [Ca(2+)](mito) responses in perinuclear and distal mitochondria. CGP-37157 and Ru360 significantly enhanced histamine-induced [Ca(2+)](cyt). TNF-α and IL-13 both increased [Ca(2+)](cyt), which was associated with decreased [Ca(2+)](mito) in the case of TNF-α but not IL-13. The effects of TNF-α on both [Ca(2+)](cyt) and [Ca(2+)](mito) were affected by CGP-37157 but not by Ru360. Overall, these data demonstrate that in human ASM cells, mitochondria buffer [Ca(2+)](cyt) after agonist stimulation and its enhancement by inflammation. The differential regulation of [Ca(2+)](mito) in different parts of ASM cells may serve to locally regulate Ca(2+) fluxes from intracellular sources versus the plasma membrane as well as respond to differential energy demands at these sites. We propose that such differential mitochondrial regulation, and its disruption, may play a role in airway hyperreactivity in diseases such as asthma, where [Ca(2+)](cyt) is increased.

show abstract

Endoplasmic Reticulum/Mitochondria Calcium Cross‐Talk

Cited by 25 publications

References 6 publications

The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore

The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore

Disorders of mitochondrial function

Inflammation alters regional mitochondrial Ca²⁺ in human airway smooth muscle cells

Contact Info

Product

Resources

About

Endoplasmic Reticulum/Mitochondria Calcium Cross‐Talk

Cited by 25 publications

References 6 publications

The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore

The C Terminus of Bax Inhibitor-1 Forms a Ca2+-permeable Channel Pore

Disorders of mitochondrial function

Inflammation alters regional mitochondrial Ca2+ in human airway smooth muscle cells

Contact Info

Product

Resources

About

Inflammation alters regional mitochondrial Ca²⁺ in human airway smooth muscle cells