The effect of ruthenium red on the uptake and release of Ca2+ by mitochondria

Rossi, C; Vasington, Frank D.; Carafoli, Ernesto

doi:10.1016/0006-291x(73)91322-3

Cited by 113 publications

(48 citation statements)

References 6 publications

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“…Our observation that Ruthenium Red did not promote the release of 45Ca from mitochondria which have been loaded with 45Ca, while in agreement with the results of Rossi et al [3], is in contradiction with the findings of Sordhal [4] and Puskin et al [5]. This contradiction could be attributed to differences in the incubation conditions e.g., both Sordhal [4] and Puskin et al [S] conducted their calcium loading of the mitochondria in the presence of a permeant anion.…”

Section: Resultssupporting

confidence: 94%

“…However, Puskin et al [S] mentioned that their Ruthenium Red-induced release of calcium from pre-loaded mitochondria occurred even in the absence of a permeant anion. The experiments of Rossi et al [3] and our experiments (see fig.3) were performed using mitochondria loaded with calcium in the absence of a permeant anion.…”

Section: Resultsmentioning

confidence: 99%

“…Other laboratories have presented evidence indicating that Ruthenium Red indeed causes the release of calcium from mitochondria pre-loaded with calcium [4,.5]. Also, it has been reported that Ruthenium Red has no effect on uncoupler-induced discharge of calcium from preloaded mitochondria [3,5]. Hence, the previous studies of the effects of Ruthenium Red on mitochondrial calcium metabolism suggest that influx but not efflux of calcium is sensitive to this compound.…”

Section: Introductionmentioning

confidence: 97%

“…Currently there seems to be general agreement regarding the inhibitory effect of Ruthenium Red on mitochondrial calcium uptake but some degree of disagreement over the effect(s) of Ruthenium Red on the efflux of calcium from mitochondria. Rossi et al [3] demonstrated that Ruthenium Red does not promote the release of calcium from mitochondria when added after the calcium uptake is complete. Other laboratories have presented evidence indicating that Ruthenium Red indeed causes the release of calcium from mitochondria pre-loaded with calcium [4,.5].…”

Section: Introductionmentioning

confidence: 99%

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The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

Luthra

Olson

1977

FEBS Letters

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Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

Luthra

Olson

1977

FEBS Letters

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“…Would Ca2+ attain electrochemical equilibrium via an electrophoretic uniport, should ruthenium red not affect the CaZ+ distribution ratio. However if ruthenium red is added in steady-state, after Ca" accumulation, calcium begins to leak out at an extent which is proportional to the degree of inhibition of the Ca2+ carrier [S, 10,12,14,15]. These considerations support the concept of steady-state…”

mentioning

confidence: 87%

ΔpH Induced Calcium Fluxes in Rat Liver Mitochondria

Bernardi¹,

Azzone²,

Veronese³

1979

European Journal of Biochemistry

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The paper reports an investigation on ΔpH‐driven Ca2+ fluxes in rotenone‐treated rat liver mitochondria. The H+ concentration gradient (acidic inside) required to drive Ca2+ influx is obtained from the K+ concentration gradient through a H+/K+ exchange. The rate of H+/K+ exchange is very low in native mitochondria and is markedly enhanced by the electroneutral ionophore nigericin. The rate of Ca2+ influx depends on the rate of generation of ΔpH; it is negligible in native mitochondria and fast after nigericin. The process of ΔpH‐driven Ca2+ influx shows three basic features. First, the rate of Ca2+ influx is markedly increased by the addition of uncouplers. Second, the rate of Ca2+ influx is inhibited by ruthenium red with the same sensitivity as the processes driven by the H+ pump or K+ diffusion. The electroneutral H+/Ca2+ ionophore A23187 restores Ca2+ influx in mitochondria inhibited by ruthenium red. Third, both rate and extent of ΔpH‐driven Ca2+ influx are inhibited by the addition of weak bases but not of weak acids. The process of ΔpH‐driven Ca2+ influx is accompanied by H+ efflux. A correlation also exists between generation of ΔpH (acidic inside) due to H+/K+ exchange and utilization of ΔpH due to H+/Ca2+ exchange. The process of ΔpH‐driven, A23187‐catalyzed, H+/Ca2+ exchange is not preceeded by rapid H+/K+ exchange in the absence of nigericin. After termination of the phase of Ca2+ influx a phase of Ca2+ efflux ensues. Ca2+ efflux is not coupled to H+ or K+ reentry and is completely inhibited by ruthenium red. Ca2+ efflux is not observed when Ca2+ transport is catalyzed by A23187 in mitochondria inhibited by ruthenium red. Furthermore A23187 abolishes Ca2+ efflux also when Ca2+ influx occurs in the absence of ruthenium red. The data suggest that the ΔpH‐driven Ca2+ influx and the subsequent Ca2+ efflux take place through the native carrier as electrical uniport.

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Biological regulatory network analysis for targeting the mitochondrial calcium uniporter (MCU) mediated calcium (Ca²⁺) transport in neurodegenerative disorders

Amjid,

Aziz,

Habib

et al. 2024

Cell Biochemistry & Function

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Calcium (Ca2+) has been observed as the most important ion involved in a series of cellular processes and its homeostasis is critical for normal cellular functions. Mitochondrial calcium uniporter (MCU) complex has been recognized as the most important calcium‐specific channel located in the inner mitochondrial membrane and is one of the major players in maintaining the Ca2+ homeostasis by transporting Ca2+ across the mitochondrial membrane. Furthermore, dysregulation of the mitochondrial Ca2+ homeostasis has been orchestrated to neurodegenerative response. This necessitates quantitative evaluation of the MCU‐dependent mROS production and subsequent cellular responses for more specific therapeutic interventions against neurodegenerative disorders. Towards this goal, here we present a biological regulatory network of MCU to dynamically simulate the MCU‐mediated ROS production and its response in neurodegeneration. Previously, ruthenium complex RuRed and its derivatives have been reported to show low nM to high µM potency against MCU to maintain cytosolic Ca2+ (cCa2+) homeostasis by modulating mitochondrial Ca2+ (mCa2+) uptake. Therefore, structural modeling and dynamic simulation of MCU pore‐forming subunit is performed to probe the interaction profiling of previously reported Ru265 and its derivatives compounds with MCU. The current study highlighted MCU as a potential drug target in neurodegenerative disorders. Furthermore, ASP261 and GLU264 amino acid residues in DIME motif of MCU pore‐forming subunits are identified as crucial for modulating the activity of MCU in neurodegenerative disorders.

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The effect of ruthenium red on the uptake and release of Ca2+ by mitochondria

Cited by 113 publications

References 6 publications

The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

ΔpH Induced Calcium Fluxes in Rat Liver Mitochondria

Biological regulatory network analysis for targeting the mitochondrial calcium uniporter (MCU) mediated calcium (Ca²⁺) transport in neurodegenerative disorders

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The effect of ruthenium red on the uptake and release of Ca2+ by mitochondria

Cited by 113 publications

References 6 publications

The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

ΔpH Induced Calcium Fluxes in Rat Liver Mitochondria

Biological regulatory network analysis for targeting the mitochondrial calcium uniporter (MCU) mediated calcium (Ca2+) transport in neurodegenerative disorders

Contact Info

Product

Resources

About

Biological regulatory network analysis for targeting the mitochondrial calcium uniporter (MCU) mediated calcium (Ca²⁺) transport in neurodegenerative disorders