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Calcium signaling around Mitochondria Associated Membranes (MAMs).

Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Giorgi C, Marchi S, Missiroli S, Poletti F, Rimessi A, Duszynski J, Wieckowski MR, Pinton P - Cell Commun. Signal (2011)

Bottom Line: Mitochondria are also major components of calcium signalling, capable of modulating both the amplitude and the spatio-temporal patterns of Ca2+ signals.In this review, we summarize the most up-to-date findings on the modulation of intracellular Ca2+ release and Ca2+ uptake mechanisms.We also explore the tight interplay between ER- and mitochondria-mediated Ca2+ signalling, covering the structural and molecular properties of the zones of close contact between these two networks.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy. paolo.pinton@unife.it.

ABSTRACT
Calcium (Ca2+) homeostasis is fundamental for cell metabolism, proliferation, differentiation, and cell death. Elevation in intracellular Ca2+ concentration is dependent either on Ca2+ influx from the extracellular space through the plasma membrane, or on Ca2+ release from intracellular Ca2+ stores, such as the endoplasmic/sarcoplasmic reticulum (ER/SR). Mitochondria are also major components of calcium signalling, capable of modulating both the amplitude and the spatio-temporal patterns of Ca2+ signals. Recent studies revealed zones of close contact between the ER and mitochondria called MAMs (Mitochondria Associated Membranes) crucial for a correct communication between the two organelles, including the selective transmission of physiological and pathological Ca2+ signals from the ER to mitochondria. In this review, we summarize the most up-to-date findings on the modulation of intracellular Ca2+ release and Ca2+ uptake mechanisms. We also explore the tight interplay between ER- and mitochondria-mediated Ca2+ signalling, covering the structural and molecular properties of the zones of close contact between these two networks.

No MeSH data available.


Related in: MedlinePlus

Representation of intracellular Ca2+ dynamics and MAMs proteins involved in ER-mitochondria Ca2+ cross-talk. A series of protein localized in MAMs (such as PML, AKT, grp-75, SIG-1R, Mfn-1/-2, BiP, AKT) regulate Ca2+ release from the ER and an efficient mitochondrial Ca2+ uptake, resulting in different functional outcomes. Cells generate Ca2+ signal through two mechanism that use internal and external sources of Ca2+. Calcium enters into the cell through channels and pumps situated on the plasma membrane; these are gated by voltage (VOCs) or external messengers (ROCs). A series of stimuli that act on cell surface receptors triggers the activation of PLC that catalyses the hydrolysis of phosphatidylinositol 4,5-biphosphate to IP3 and DAG. The binding of IP3 to its receptor IP3R stimulates ER Ca2+ release and consequently the transfer of Ca2+ (red dots) from ER to mitochondria. Mitochondrial surface directly interacts with the ER through contact sites defining hotspot Ca2+ signalling units. Mitochondrial Ca2+ import occurs through the mitochondrial Ca2+ uniporter (MCU) and the H+/Ca2+ exchanger LETM1; conversely, NCLX, mitochondrial Na+/Ca2+ exchanger, together with the PTP, export Ca2+ from the matrix. Ca2+ levels return to resting conditions through a series of channels and pumps: PMCA and NCX permit the ion extrusion into the extracellular milieu, SERCA (situated on the ER) and SPCA (on the Golgi apparatus) re-establish basal Ca2+ levels in intracellular stores. Abbreviations: ANT, adenosine nucleoside transporter; ETC, electron transport chain; HK, hexokinase; CD, cyclophilin D; CK, creatine kinase; BR, benzodiazepine receptor.
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Figure 1: Representation of intracellular Ca2+ dynamics and MAMs proteins involved in ER-mitochondria Ca2+ cross-talk. A series of protein localized in MAMs (such as PML, AKT, grp-75, SIG-1R, Mfn-1/-2, BiP, AKT) regulate Ca2+ release from the ER and an efficient mitochondrial Ca2+ uptake, resulting in different functional outcomes. Cells generate Ca2+ signal through two mechanism that use internal and external sources of Ca2+. Calcium enters into the cell through channels and pumps situated on the plasma membrane; these are gated by voltage (VOCs) or external messengers (ROCs). A series of stimuli that act on cell surface receptors triggers the activation of PLC that catalyses the hydrolysis of phosphatidylinositol 4,5-biphosphate to IP3 and DAG. The binding of IP3 to its receptor IP3R stimulates ER Ca2+ release and consequently the transfer of Ca2+ (red dots) from ER to mitochondria. Mitochondrial surface directly interacts with the ER through contact sites defining hotspot Ca2+ signalling units. Mitochondrial Ca2+ import occurs through the mitochondrial Ca2+ uniporter (MCU) and the H+/Ca2+ exchanger LETM1; conversely, NCLX, mitochondrial Na+/Ca2+ exchanger, together with the PTP, export Ca2+ from the matrix. Ca2+ levels return to resting conditions through a series of channels and pumps: PMCA and NCX permit the ion extrusion into the extracellular milieu, SERCA (situated on the ER) and SPCA (on the Golgi apparatus) re-establish basal Ca2+ levels in intracellular stores. Abbreviations: ANT, adenosine nucleoside transporter; ETC, electron transport chain; HK, hexokinase; CD, cyclophilin D; CK, creatine kinase; BR, benzodiazepine receptor.

Mentions: In this review, we attempt to give a condensed overview of the molecular aspects of intracellular calcium homeostasis, with special emphasis on the structural and molecular aspects of the ER (main intracellular Ca2+ stores), mitochondria (possessors of a series of complex systems for the influx/efflux of Ca2+) and MAMs (covering important roles in various cellular 'housekeeping' functions, including Ca2+ signalling) (Figure 1).


Calcium signaling around Mitochondria Associated Membranes (MAMs).

Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Giorgi C, Marchi S, Missiroli S, Poletti F, Rimessi A, Duszynski J, Wieckowski MR, Pinton P - Cell Commun. Signal (2011)

Representation of intracellular Ca2+ dynamics and MAMs proteins involved in ER-mitochondria Ca2+ cross-talk. A series of protein localized in MAMs (such as PML, AKT, grp-75, SIG-1R, Mfn-1/-2, BiP, AKT) regulate Ca2+ release from the ER and an efficient mitochondrial Ca2+ uptake, resulting in different functional outcomes. Cells generate Ca2+ signal through two mechanism that use internal and external sources of Ca2+. Calcium enters into the cell through channels and pumps situated on the plasma membrane; these are gated by voltage (VOCs) or external messengers (ROCs). A series of stimuli that act on cell surface receptors triggers the activation of PLC that catalyses the hydrolysis of phosphatidylinositol 4,5-biphosphate to IP3 and DAG. The binding of IP3 to its receptor IP3R stimulates ER Ca2+ release and consequently the transfer of Ca2+ (red dots) from ER to mitochondria. Mitochondrial surface directly interacts with the ER through contact sites defining hotspot Ca2+ signalling units. Mitochondrial Ca2+ import occurs through the mitochondrial Ca2+ uniporter (MCU) and the H+/Ca2+ exchanger LETM1; conversely, NCLX, mitochondrial Na+/Ca2+ exchanger, together with the PTP, export Ca2+ from the matrix. Ca2+ levels return to resting conditions through a series of channels and pumps: PMCA and NCX permit the ion extrusion into the extracellular milieu, SERCA (situated on the ER) and SPCA (on the Golgi apparatus) re-establish basal Ca2+ levels in intracellular stores. Abbreviations: ANT, adenosine nucleoside transporter; ETC, electron transport chain; HK, hexokinase; CD, cyclophilin D; CK, creatine kinase; BR, benzodiazepine receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198985&req=5

Figure 1: Representation of intracellular Ca2+ dynamics and MAMs proteins involved in ER-mitochondria Ca2+ cross-talk. A series of protein localized in MAMs (such as PML, AKT, grp-75, SIG-1R, Mfn-1/-2, BiP, AKT) regulate Ca2+ release from the ER and an efficient mitochondrial Ca2+ uptake, resulting in different functional outcomes. Cells generate Ca2+ signal through two mechanism that use internal and external sources of Ca2+. Calcium enters into the cell through channels and pumps situated on the plasma membrane; these are gated by voltage (VOCs) or external messengers (ROCs). A series of stimuli that act on cell surface receptors triggers the activation of PLC that catalyses the hydrolysis of phosphatidylinositol 4,5-biphosphate to IP3 and DAG. The binding of IP3 to its receptor IP3R stimulates ER Ca2+ release and consequently the transfer of Ca2+ (red dots) from ER to mitochondria. Mitochondrial surface directly interacts with the ER through contact sites defining hotspot Ca2+ signalling units. Mitochondrial Ca2+ import occurs through the mitochondrial Ca2+ uniporter (MCU) and the H+/Ca2+ exchanger LETM1; conversely, NCLX, mitochondrial Na+/Ca2+ exchanger, together with the PTP, export Ca2+ from the matrix. Ca2+ levels return to resting conditions through a series of channels and pumps: PMCA and NCX permit the ion extrusion into the extracellular milieu, SERCA (situated on the ER) and SPCA (on the Golgi apparatus) re-establish basal Ca2+ levels in intracellular stores. Abbreviations: ANT, adenosine nucleoside transporter; ETC, electron transport chain; HK, hexokinase; CD, cyclophilin D; CK, creatine kinase; BR, benzodiazepine receptor.
Mentions: In this review, we attempt to give a condensed overview of the molecular aspects of intracellular calcium homeostasis, with special emphasis on the structural and molecular aspects of the ER (main intracellular Ca2+ stores), mitochondria (possessors of a series of complex systems for the influx/efflux of Ca2+) and MAMs (covering important roles in various cellular 'housekeeping' functions, including Ca2+ signalling) (Figure 1).

Bottom Line: Mitochondria are also major components of calcium signalling, capable of modulating both the amplitude and the spatio-temporal patterns of Ca2+ signals.In this review, we summarize the most up-to-date findings on the modulation of intracellular Ca2+ release and Ca2+ uptake mechanisms.We also explore the tight interplay between ER- and mitochondria-mediated Ca2+ signalling, covering the structural and molecular properties of the zones of close contact between these two networks.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy. paolo.pinton@unife.it.

ABSTRACT
Calcium (Ca2+) homeostasis is fundamental for cell metabolism, proliferation, differentiation, and cell death. Elevation in intracellular Ca2+ concentration is dependent either on Ca2+ influx from the extracellular space through the plasma membrane, or on Ca2+ release from intracellular Ca2+ stores, such as the endoplasmic/sarcoplasmic reticulum (ER/SR). Mitochondria are also major components of calcium signalling, capable of modulating both the amplitude and the spatio-temporal patterns of Ca2+ signals. Recent studies revealed zones of close contact between the ER and mitochondria called MAMs (Mitochondria Associated Membranes) crucial for a correct communication between the two organelles, including the selective transmission of physiological and pathological Ca2+ signals from the ER to mitochondria. In this review, we summarize the most up-to-date findings on the modulation of intracellular Ca2+ release and Ca2+ uptake mechanisms. We also explore the tight interplay between ER- and mitochondria-mediated Ca2+ signalling, covering the structural and molecular properties of the zones of close contact between these two networks.

No MeSH data available.


Related in: MedlinePlus