Dysregulation of RyR Calcium Channel and Impaired Mitochondrial Calcium Uptake Cause the Onset of Mitochondrial Retrograde Signaling

2020 ◽  
Author(s):  
Anindya Roy Chowdhury ◽  
Satish Srinivasan ◽  
György Csordás ◽  
György Hajnóczky ◽  
Narayan Avadhani
Keyword(s):  
Calcium Channel ◽  
Calcium Uptake ◽  
Retrograde Signaling ◽  
Mitochondrial Calcium ◽  
Mitochondrial Retrograde Signaling ◽  
Mitochondrial Calcium Uptake

Dinuclear nitrido-bridged ruthenium complexes bearing diimine ligands

2017 ◽  
Vol 46 (41) ◽  
pp. 14256-14263 ◽  
Author(s):  
Julie Urgiles ◽  
Sarah R. Nathan ◽  
Samantha N. MacMillan ◽  
Justin J. Wilson
Keyword(s):  
Calcium Uptake ◽  
Ruthenium Complexes ◽  
Ligand Substitution ◽  
Mitochondrial Calcium ◽  
Substitution Reactions ◽  
Uptake Inhibition ◽  
Diimine Ligands ◽  
Mitochondrial Calcium Uptake ◽  
Ligand Substitution Reactions

Nitrido-bridged ruthenium complexes are synthesized via ligand substitution reactions and evaluated for mitochondrial calcium uptake inhibition.

Mitochondrial calcium uptake during ischemia is regulated by cytosolic ATP:ADP ratio

2003 ◽  
Vol 114 (2) ◽  
pp. 304 ◽  
Author(s):  
A. Wakata ◽  
A.E. Belous ◽  
C.D. Knox ◽  
J.M. Pierce ◽  
I.B. Nicoud ◽  
...  
Keyword(s):  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Mitochondrial Calcium Uptake

OXYGEN AND MITOCHONDRIAL CALCIUM UPTAKE CAPACITY REGULATE THE INCIDENCE OF APOPTOSIS IN EPITHELIAL CELLS

Shock ◽  
2004 ◽  
Vol 21 (Supplement) ◽  
pp. 28
Author(s):  
Xueling Ma ◽  
Stefan Baeder ◽  
Weidong Du ◽  
Marion E. Schneider
Keyword(s):  
Epithelial Cells ◽  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Uptake Capacity ◽  
Mitochondrial Calcium Uptake

Abstract 284: Loss of Micu3 Confers Cardioprotection Against Cardiac Injury

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Bao Puente ◽  
Junhui Sun ◽  
Maria Fergusson ◽  
Julia Liu ◽  
Anna Kosmach ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Calcium Uptake ◽  
Cardiac Injury ◽  
Mitochondrial Calcium ◽  
Wild Type ◽  
Ischemic Reperfusion ◽  
Mitochondrial Calcium Uptake

Background: Mitochondrial calcium flux and signaling is integral to cardiac function and contraction. However, during pathologic conditions such as ischemic/reperfusion injury, mitochondrial calcium overload can induce the opening of the mitochondrial permeability transitioning pore (PTP), resulting in the collapse of mitochondrial membrane potential, ATP depletion, and generation of reactive oxygen species, all together leading to cell death. Hence, modulation of mitochondrial calcium and inhibition of the PTP is a promising target for cardioprotection and prevention of cardiomyocyte death. The mitochondrial calcium uniporter (MCU) complex mediates rapid mitochondrial calcium uptake. MICU3 is a regulator of the MCU complex and has been shown to be a highly potent stimulator of MCU-dependent calcium uptake in neuronal cells. We found that MICU3 is expressed in hearts and we therefore investigated the role of MICU3 in the heart. We examined the role of MICU3 in the development of hypertrophy and in a separate study we examined the response to ischemic-reperfusion (I/R) injury. Given its role in regulating mitochondrial calcium uptake, we hypothesized that loss of MICU3 confers protection against cardiac injury. Methods: Mice with global deletion of Micu3 (Micu3 -/- ) were created utilizing CRISPR-Cas9 technology. Adult knockout and littermate wild type mice were treated with Isoproterenol (15mg/kg/day) for two weeks to induce hypertrophy. Echocardiograms were performed at baseline and after treatment to assess changes in left ventricular size and function. I/R injury was studied using Langendorff ex vivo perfused heart system, exposing knockout and wild type hearts to 20 minutes of ischemia and 90 minutes of reperfusion. Hemodynamic data and infarct size were collected and compared. Student t-test and 2-way ANOVA were used for statistical analysis. Result: Micu3 -/- mice had normal cardiac function at baseline. There was no sex difference in cardiac function. Micu3 -/- mice continued to show normal function after 2 weeks of treatment with Isoproterenol, whereas wild type mice exhibited depressed function (median FS 35% vs. 24% p = 0.0001, EF 64% vs. 50% p = 0.0001). Wild type mice developed LV dilation from baseline (median 4.15mm vs. 4.57mm, p = 0.0014), whereas LV dimension remained stable in Micu3 -/- mice (median 4.12mm vs. 4.18mm, p= 0.9892). Micu3 - /- mice were also protected from I/R injury. Compared to wild types, Micu3 -/- hearts demonstrated less contractile dysfunction at end reperfusion (median rate pressure product 62% vs. 41%, p = 0.002), and significantly smaller infarct size (median 33% vs. 53%, p = 0.0001). Conclusion: Loss of MICU3 confers cardioprotection against ischemic reperfusion injury and Isoproterenol induced cardiac dysfunction.

Protection of mitochondrial function by mannitol in ischemic acute renal failure

1984 ◽  
Vol 247 (2) ◽  
pp. F365-F369 ◽  
Author(s):  
R. W. Schrier ◽  
P. E. Arnold ◽  
J. A. Gordon ◽  
T. J. Burke
Keyword(s):  
Calcium Uptake ◽  
Cellular Level ◽  
Cell Swelling ◽  
Mitochondrial Calcium ◽  
Release Rates ◽  
Ischemic Insult ◽  
Cellular Protection ◽  
Functional Changes ◽  
Mitochondrial Calcium Uptake ◽  
Ischemic Acute Renal Failure

The effect of isotonic mannitol to provide protection against ischemic renal injury was examined in the dog. Mannitol treatment attenuated the fall in glomerular filtration rate at both 1 and 24 h after the ischemic insult. The functional changes were associated with profound cellular protection, since normal mitochondrial respiration, mitochondrial calcium uptake and release rates were preserved, and excessive mitochondrial calcium accumulation was prevented. These effects at the cellular level appear critical to the protective effect of mannitol after ischemia and are most likely due to prevention of cell swelling.

scholarly journals Buffer Magnesium Limits Mitochondrial Calcium Uptake but not Matrix Calcium Buffering in Response to ADP

2010 ◽  
Vol 98 (3) ◽  
pp. 736a
Author(s):  
Age D. Boelens ◽  
Ranjan K. Dash ◽  
Johan Haumann ◽  
Amadou K.S. Camara ◽  
Mohammed Aldakkak ◽  
...  
Keyword(s):  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Calcium Buffering ◽  
Mitochondrial Calcium Uptake

scholarly journals Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks

2015 ◽  
Vol 28 (11) ◽  
pp. 1579-1588 ◽  
Author(s):  
Sridhar S. Kannurpatti ◽  
Basavaraju G. Sanganahalli ◽  
Peter Herman ◽  
Fahmeed Hyder
Keyword(s):  
Resting State ◽  
Calcium Uptake ◽  
Brain Networks ◽  
Resting State Fmri ◽  
Mitochondrial Calcium ◽  
Mitochondrial Calcium Uptake

scholarly journals Ucp2 Modulates Cellular Excitation Contraction Coupling via Mitochondrial Calcium Uptake

2014 ◽  
Vol 106 (2) ◽  
pp. 593a ◽  
Author(s):  
Robert K. Larbig ◽  
Lukas J. Motloch ◽  
Tina Gebing ◽  
Sara Reda ◽  
Eva Deininger ◽  
...  
Keyword(s):  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Mitochondrial Calcium Uptake
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