Calcium stimulates ATP-Mg/Pi carrier activity in rat liver mitochondria.

Nosek, Michael T.; Dransfield, Daniel T.; Aprille, June R.

doi:10.1016/s0021-9258(19)38908-2

Cited by 62 publications

(2 citation statements)

References 33 publications

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“…Of the Ca 2+ sensitive transporters, the aspartate/glutamate exchangers, citrin and aralar, are the best characterized, 57−59 along with the ATP-Mg/P i carrier (sCaMC). 60,61 These transporters belong to the carrier family with EF-hand Ca 2+ -binding motifs on the external membrane N-terminal domains. Through these mechanisms, Ca 2+ c can directly impact the transport of redox elements and the net ATP content of the matrix and can potentially impact cellular signaling through cytosolic amino acid levels.…”

Section: ■ Isolated Enzyme Studiesmentioning

confidence: 99%

“…Another important element in the interaction of Ca 2+ with metabolic events is the impact on substrate transport (see ref for a review). Of the Ca 2+ sensitive transporters, the aspartate/glutamate exchangers, citrin and aralar, are the best characterized, − along with the ATP-Mg/P i carrier (sCaMC). , These transporters belong to the carrier family with EF-hand Ca 2+ -binding motifs on the external membrane N-terminal domains. Through these mechanisms, Ca 2+ c can directly impact the transport of redox elements and the net ATP content of the matrix and can potentially impact cellular signaling through cytosolic amino acid levels. , It has been proposed that the activation of sCaMC may be involved in the regulation of ATP synthesis with work in the heart; however, how an increase in the influx of ATP into the matrix would support ATP production is unclear other than increasing the net concentration of adenylates and perhaps improving the kinetic driving force for Complex V.…”

Section: Isolated Enzyme Studiesmentioning

confidence: 99%

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Role of Mitochondrial Ca²⁺ in the Regulation of Cellular Energetics

2012

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Calcium is an important signaling molecule involved in the regulation of many cellular functions. The large free energy in the Ca2+ ion membrane gradients make Ca2+ signaling inherently sensitive to the available cellular free energy, primarily in the form of ATP. In addition, Ca2+ regulates many cellular ATP consuming reactions such as muscle contraction, exocytosis, biosynthesis and neuronal signaling. Thus, Ca2+ becomes a logical candidate as a signaling molecule to modulate ATP hydrolysis and synthesis during changes in numerous forms of cellular work. Mitochondria are the primary source of aerobic energy production in mammalian cells and also maintain a large Ca2+ gradient across their inner membrane providing a signaling potential for this molecule. The demonstrated link between cytosolic and mitochondrial [Ca2+], identification of transport mechanisms as well as proximity of mitochondria to Ca2+ release sites further supports the notion that Ca2+ can be an important signaling molecule in the energy metabolism interplay of the cytosol with the mitochondria. Here we review sites within the mitochondria where Ca2+ plays a role in the regulation of ATP generation and potentially contributes to the orchestration of the cellular metabolic homeostasis. Early work on isolated enzymes pointed to several matrix dehydrogenases that are stimulated by Ca2+, which were confirmed in the intact mitochondrion as well as cellular and in vivo systems. However, studies in these intact systems suggested a more expansive influence of Ca2+ on mitochondrial energy conversion. Numerous non-invasive approaches monitoring NADH, mitochondrial membrane potential, oxygen consumption and workloads suggest significant Ca2+ effects on other elements of NADH generation as well as downstream elements of oxidative phosphorylation including the F1FO-ATPase and the cytochrome chain. These other potential elements of Ca2+ modification of mitochondrial energy conversion will be the focus of this review. Though most of specific molecular mechanisms have yet to be elucidated, it is clear that Ca2+ provides a balanced activation of mitochondrial energy metabolism which exceeds the alteration of dehydrogenases alone.

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Section: ■ Isolated Enzyme Studiesmentioning

confidence: 99%

Section: Isolated Enzyme Studiesmentioning

confidence: 99%

Role of Mitochondrial Ca²⁺ in the Regulation of Cellular Energetics

2012

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Calcium‐regulated mitochondrial ATP‐Mg/P_i carriers evolved from a fusion of an EF‐hand regulatory domain with a mitochondrial ADP/ATP carrier‐like domain

Harborne

Kunji

2018

IUBMB Life

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The mitochondrial ATP‐Mg/Pi carrier is responsible for the calcium‐dependent regulation of adenosine nucleotide concentrations in the mitochondrial matrix, which allows mitochondria to respond to changing energy requirements of the cell. The carrier is expressed in mitochondria of fungi, plants and animals and belongs to the family of mitochondrial carriers. The carrier is unusual as it consists of three separate domains: (i) an N‐terminal regulatory domain with four calcium‐binding EF‐hands similar to calmodulin, (ii) a loop domain containing an amphipathic α‐helix and (iii) a mitochondrial carrier domain related to the mitochondrial ADP/ATP carrier. This striking example of three domains coming together from different origins to provide new functions represents an interesting quirk of evolution. In this review, we outline how the carrier was identified and how its physiological role was established with a focus on human isoforms. We exploit the sequence and structural information of the domains to explore the similarities and differences to their closest counterparts; mitochondrial ADP/ATP carriers and proteins with four EF‐hands. We discuss how their combined function has led to a mechanism for calcium‐regulated transport of adenosine nucleotides. Finally, we compare the ATP‐Mg/Pi carrier with the mitochondrial aspartate/glutamate carrier, the only other mitochondrial carrier regulated by calcium, and we will argue that they have arisen by convergent rather than divergent evolution. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(12):1222–1232, 2018

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Glutamate‐induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons

Shindo¹,

Fujimoto²,

Hotta³

et al. 2010

J of Neuroscience Research

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Excess administration of glutamate is known to induce Ca(2+) overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg(2+) in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg(2+) in the excitotoxicity, we simultaneously measured intracellular Ca(2+) and Mg(2+), using fluorescent dyes, Fura red, a fluorescent Ca(2+) probe, and KMG-104, a highly selective fluorescent Mg(2+) probe developed by our group, respectively. Administration of 100 μM glutamate supplemented with 10 μM glycine to rat hippocampal neurons induced an increase in intracellular Mg(2+) concentration ([Mg(2+)](i)). Extracellular Mg(2+) was not required for this glutamate-induced increase in [Mg(2+)](i), and no increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) or [Mg(2+)](i) was observed in neurons in nominally Ca(2+)-free medium. Application of 5 μM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca(2+)](i) and [Mg(2+)](i). Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg(2+)](i) but did induce an additive increase in [Ca(2+)](i). Moreover, the glutamate-induced increase in [Mg(2+)](i) was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg(2+) efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca(2+) uniporter, prevented this [Mg(2+)](i) increase. These results indicate that glutamate-induced increases in [Mg(2+)](i) result from the Mg(2+) release from mitochondria and that Ca(2+) accumulation in the mitochondria is required for this Mg(2+) release.

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Calcium stimulates ATP-Mg/Pi carrier activity in rat liver mitochondria.

Cited by 62 publications

References 33 publications

Role of Mitochondrial Ca²⁺ in the Regulation of Cellular Energetics

Role of Mitochondrial Ca²⁺ in the Regulation of Cellular Energetics

Calcium‐regulated mitochondrial ATP‐Mg/P_i carriers evolved from a fusion of an EF‐hand regulatory domain with a mitochondrial ADP/ATP carrier‐like domain

Glutamate‐induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons

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Calcium stimulates ATP-Mg/Pi carrier activity in rat liver mitochondria.

Cited by 62 publications

References 33 publications

Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics

Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics

Calcium‐regulated mitochondrial ATP‐Mg/Pi carriers evolved from a fusion of an EF‐hand regulatory domain with a mitochondrial ADP/ATP carrier‐like domain

Glutamate‐induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons

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Role of Mitochondrial Ca²⁺ in the Regulation of Cellular Energetics

Role of Mitochondrial Ca²⁺ in the Regulation of Cellular Energetics

Calcium‐regulated mitochondrial ATP‐Mg/P_i carriers evolved from a fusion of an EF‐hand regulatory domain with a mitochondrial ADP/ATP carrier‐like domain