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Calcium and ROS: A mutual interplay.

Görlach A, Bertram K, Hudecova S, Krizanova O - Redox Biol (2015)

Bottom Line: Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions.Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death.However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders.

View Article: PubMed Central - PubMed

Affiliation: Experimental and Molecular Pediatric Cardiology, German Heart Center Munich at the Technical University Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. Electronic address: goerlach@dhm.mhn.de.

No MeSH data available.


Related in: MedlinePlus

Calcium and ROS crosstalk between endoplasmic reticulum and mitochondria. The endoplasmic reticulum (ER) is a major site of calcium storage. Calcium from ER cisternae is flowing mainly through calcium release channels as inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR). These channels are accumulated in mitochondrial associated membranes (MAMs), which associate with the mitochondrial outer membrane. Calcium ions from the cytoplasm enter the mitochondria through voltage dependent anion channels (VDAC) or calcium uniporter. High levels of calcium stimulate respiratory chain activity leading to higher amounts of reactive oxygen species (ROS). ROS can further target ER-based calcium channels leading to increased release of calcium and further increased ROS levels. Increased ROS and calcium load can open the mitochondrial permeability transition pore (mPTP) resulting in the release of pro-apoptotic factors. Abbreviations: SERCA – sarco/endoplasmic reticulum Ca2+ ATPase; RyR – ryanodine receptors; IP3R – IP3 receptor; VDAC – voltage-dependent anion channel; ANT – adenine-nucleotide transporter; mPTP – mitochondrial permeability transition pore; mNCX – mitochondrial sodium/calcium exchanger.
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f0010: Calcium and ROS crosstalk between endoplasmic reticulum and mitochondria. The endoplasmic reticulum (ER) is a major site of calcium storage. Calcium from ER cisternae is flowing mainly through calcium release channels as inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR). These channels are accumulated in mitochondrial associated membranes (MAMs), which associate with the mitochondrial outer membrane. Calcium ions from the cytoplasm enter the mitochondria through voltage dependent anion channels (VDAC) or calcium uniporter. High levels of calcium stimulate respiratory chain activity leading to higher amounts of reactive oxygen species (ROS). ROS can further target ER-based calcium channels leading to increased release of calcium and further increased ROS levels. Increased ROS and calcium load can open the mitochondrial permeability transition pore (mPTP) resulting in the release of pro-apoptotic factors. Abbreviations: SERCA – sarco/endoplasmic reticulum Ca2+ ATPase; RyR – ryanodine receptors; IP3R – IP3 receptor; VDAC – voltage-dependent anion channel; ANT – adenine-nucleotide transporter; mPTP – mitochondrial permeability transition pore; mNCX – mitochondrial sodium/calcium exchanger.

Mentions: Generation of ROS by mitochondria has been considered for a long time to be only a byproduct of oxidative metabolism in the course of ATP production [151,164]. However, clear evidence exists that mitochondrial ROS might also have a function in signaling within mitochondria or between mitochondria and other organelles [130,34]. Under normal conditions, up to 1% of the electrons flowing to molecular oxygen through the electron transport chain may be diverted to form superoxide. Superoxide can be generated at different sites within the mitochondria [22]. Among them, the ubiquinone-binding sites in complex I (site IQ) and complex III (site IIIQo) of the respiratory chain, glycerol 3-phosphate dehydrogenase, the flavin in complex I (site IF), the electron transferring flavoprotein:Q oxidoreductase (ETFQOR) of fatty acid beta-oxidation, and pyruvate and 2-oxoglutarate dehydrogenases have the highest capacity to generate superoxide. Interestingly, only site IIIQo (on complex III) and glycerol 3-phosphate dehydrogenase can release superoxide into the intermembrane space suggesting that these sites are of a high importance of mitochondrial ROS release into the cytosol ([102], Fig. 2).


Calcium and ROS: A mutual interplay.

Görlach A, Bertram K, Hudecova S, Krizanova O - Redox Biol (2015)

Calcium and ROS crosstalk between endoplasmic reticulum and mitochondria. The endoplasmic reticulum (ER) is a major site of calcium storage. Calcium from ER cisternae is flowing mainly through calcium release channels as inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR). These channels are accumulated in mitochondrial associated membranes (MAMs), which associate with the mitochondrial outer membrane. Calcium ions from the cytoplasm enter the mitochondria through voltage dependent anion channels (VDAC) or calcium uniporter. High levels of calcium stimulate respiratory chain activity leading to higher amounts of reactive oxygen species (ROS). ROS can further target ER-based calcium channels leading to increased release of calcium and further increased ROS levels. Increased ROS and calcium load can open the mitochondrial permeability transition pore (mPTP) resulting in the release of pro-apoptotic factors. Abbreviations: SERCA – sarco/endoplasmic reticulum Ca2+ ATPase; RyR – ryanodine receptors; IP3R – IP3 receptor; VDAC – voltage-dependent anion channel; ANT – adenine-nucleotide transporter; mPTP – mitochondrial permeability transition pore; mNCX – mitochondrial sodium/calcium exchanger.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556774&req=5

f0010: Calcium and ROS crosstalk between endoplasmic reticulum and mitochondria. The endoplasmic reticulum (ER) is a major site of calcium storage. Calcium from ER cisternae is flowing mainly through calcium release channels as inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR). These channels are accumulated in mitochondrial associated membranes (MAMs), which associate with the mitochondrial outer membrane. Calcium ions from the cytoplasm enter the mitochondria through voltage dependent anion channels (VDAC) or calcium uniporter. High levels of calcium stimulate respiratory chain activity leading to higher amounts of reactive oxygen species (ROS). ROS can further target ER-based calcium channels leading to increased release of calcium and further increased ROS levels. Increased ROS and calcium load can open the mitochondrial permeability transition pore (mPTP) resulting in the release of pro-apoptotic factors. Abbreviations: SERCA – sarco/endoplasmic reticulum Ca2+ ATPase; RyR – ryanodine receptors; IP3R – IP3 receptor; VDAC – voltage-dependent anion channel; ANT – adenine-nucleotide transporter; mPTP – mitochondrial permeability transition pore; mNCX – mitochondrial sodium/calcium exchanger.
Mentions: Generation of ROS by mitochondria has been considered for a long time to be only a byproduct of oxidative metabolism in the course of ATP production [151,164]. However, clear evidence exists that mitochondrial ROS might also have a function in signaling within mitochondria or between mitochondria and other organelles [130,34]. Under normal conditions, up to 1% of the electrons flowing to molecular oxygen through the electron transport chain may be diverted to form superoxide. Superoxide can be generated at different sites within the mitochondria [22]. Among them, the ubiquinone-binding sites in complex I (site IQ) and complex III (site IIIQo) of the respiratory chain, glycerol 3-phosphate dehydrogenase, the flavin in complex I (site IF), the electron transferring flavoprotein:Q oxidoreductase (ETFQOR) of fatty acid beta-oxidation, and pyruvate and 2-oxoglutarate dehydrogenases have the highest capacity to generate superoxide. Interestingly, only site IIIQo (on complex III) and glycerol 3-phosphate dehydrogenase can release superoxide into the intermembrane space suggesting that these sites are of a high importance of mitochondrial ROS release into the cytosol ([102], Fig. 2).

Bottom Line: Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions.Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death.However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders.

View Article: PubMed Central - PubMed

Affiliation: Experimental and Molecular Pediatric Cardiology, German Heart Center Munich at the Technical University Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. Electronic address: goerlach@dhm.mhn.de.

No MeSH data available.


Related in: MedlinePlus