CRYAB and HSPB2 deficiency increases myocyte mitochondrial permeability transition and mitochondrial calcium uptake

2006 ◽  
Vol 40 (6) ◽  
pp. 783-789 ◽  
Author(s):  
Toshie Kadono ◽  
Xiu Quan Zhang ◽  
Sathya Srinivasan ◽  
Hideyuki Ishida ◽  
William H. Barry ◽  
...  
Keyword(s):  
Calcium Uptake ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Calcium ◽  
Mitochondrial Permeability ◽  
Mitochondrial Calcium Uptake

scholarly journals Regulation of Kidney Mitochondrial Function by Caloric Restriction

2021 ◽  
Author(s):  
Julian DC Serna ◽  
Andressa G Amaral ◽  
Camille C Caldeira da Silva ◽  
Ana C Bonassa ◽  
Sergio L Menezes ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Calcium Homeostasis ◽  
Mitochondrial Function ◽  
Calcium Uptake ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition ◽  
Mitochondrial Calcium ◽  
Mitochondrial Permeability ◽  
Uptake Rates

Caloric restriction (CR) prevents obesity, promotes healthy aging, and increases resilience against several pathological stimuli in laboratory rodents. At the mitochondrial level, protection promoted by CR in the brain and liver is related to higher calcium uptake rates and capacities, avoiding Ca2+-induced mitochondrial permeability transition. Dietary restriction has also been shown to increase kidney resistance against damaging stimuli such as ischemia/reperfusion, but if these effects are related to similar mitochondrial adaptations had not yet been uncovered. Here, we characterized changes in mitochondrial function in response to six months of CR in rats, measuring bioenergetic parameters, redox balance and calcium homeostasis. CR promoted an increase in mitochondrial oxygen consumption rates under non-phosphorylating and uncoupled conditions. While CR prevents mitochondrial reactive oxygen species production in many tissues, in kidney we found that mitochondrial H2O2 release was enhanced, although levels of carbonylated proteins and methionine sulfoxide were unchanged. Surprisingly, and opposite to the effects observed in brain and liver, mitochondria from CR animals are more prone to Ca2+-induced mitochondrial permeability transition. CR mitochondria also displayed higher calcium uptake rates, which were not accompanied by changes in calcium efflux rates, nor related to altered inner mitochondrial membrane potentials or the amounts of the mitochondrial calcium uniporter (MCU). Instead, increased mitochondrial calcium uptake rates in CR kidneys correlate with a loss of MICU2, an MCU modulator. Interestingly, MICU2 is also modulated by CR in liver, suggesting it has a broader diet-sensitive regulatory role controlling mitochondrial calcium homeostasis. Together, our results highlight the organ-specific bioenergetic, redox, and ionic transport effects of CR. Specifically, we describe the regulation of the expression of MICU2 and its effects on mitochondrial calcium transport as a novel and interesting aspect of the metabolic responses to dietary interventions.

scholarly journals Mitochondrial calcium signalling and neurodegenerative diseases

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Elena Britti ◽  
Fabien Delaspre ◽  
Jordi Tamarit ◽  
Joaquim Ros
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Friedreich Ataxia ◽  
Calcium Signalling ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cytosolic Calcium ◽  
Mitochondrial Calcium ◽  
Atp Production ◽  
Calcium Buffering ◽  
Mitochondrial Calcium Uptake

Calcium is utilised by cells in signalling and in regulating ATP production; it also contributes to cell survival and, when concentrations are unbalanced, triggers pathways for cell death. Mitochondria contribute to calcium buffering, meaning that mitochondrial calcium uptake and release is intimately related to cytosolic calcium concentrations. This review focuses on the proteins contributing to mitochondrial calcium homoeostasis, the roles of the mitochondrial permeability transition pore (MPTP) and mitochondrial calcium-activated proteins, and their relevance in neurodegenerative pathologies. It also covers alterations to calcium homoeostasis in Friedreich ataxia (FA).

scholarly journals The Valosin-Containing Protein Protects the Heart Against Pathological Ca2+ Overload by Modulating Ca2+ Uptake Proteins

2019 ◽  
Vol 171 (2) ◽  
pp. 473-484 ◽  
Author(s):  
Shaunrick Stoll ◽  
Jing Xi ◽  
Ben Ma ◽  
Christiana Leimena ◽  
Erik J Behringer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Atp Depletion ◽  
Mitochondrial Calcium ◽  
Mptp Opening ◽  
Mitochondrial Calcium Uptake

Abstract Stress-induced mitochondrial calcium (Ca2+) overload is a key cellular toxic effectors and a trigger of cardiomyocyte death during cardiac ischemic injury through the opening of mitochondrial permeability transition pore (mPTP). We previously found that the valosin-containing protein (VCP), an ATPase-associated protein, protects cardiomyocytes against stress-induced death and also inhibits mPTP opening in vitro. However, the underlying molecular mechanisms are not fully understood. Here, we tested our hypothesis that VCP acts as a novel regulator of mitochondrial Ca2+ uptake proteins and resists cardiac mitochondrial Ca2+ overload by modulating mitochondrial Ca2+ homeostasis. By using a cardiac-specific transgenic (TG) mouse model in which VCP is overexpressed by 3.5 folds in the heart compared to the wild type (WT) mouse, we found that, under the pathological extra-mitochondrial Ca2+ overload, Ca2+ entry into cardiac mitochondria was reduced in VCP TG mice compared to their little-matched WT mice, subsequently preventing mPTP opening and ATP depletion under the Ca2+ challenge. Mechanistically, overexpression of VCP in the heart resulted in post-translational protein degradation of the mitochondrial Ca2+ uptake protein 1, an activator of the mitochondria Ca2+ uniporter that is responsible for mitochondrial calcium uptake. Together, our results reveal a new regulatory role of VCP in cardiac mitochondrial Ca2+ homeostasis and unlock the potential mechanism by which VCP confers its cardioprotection.

scholarly journals Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition

2016 ◽  
Vol 113 (13) ◽  
pp. E1872-E1880 ◽  
Author(s):  
Dipayan Chaudhuri ◽  
Daniel J. Artiga ◽  
Sunday A. Abiria ◽  
David E. Clapham
Keyword(s):  
Mammalian Cells ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Calcium ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Permeability ◽  
Calcium Uniporter ◽  
Differential Behavior ◽  
Cardiac Pathophysiology ◽  
Large Channel

During the mitochondrial permeability transition, a large channel in the inner mitochondrial membrane opens, leading to the loss of multiple mitochondrial solutes and cell death. Key triggers include excessive reactive oxygen species and mitochondrial calcium overload, factors implicated in neuronal and cardiac pathophysiology. Examining the differential behavior of mitochondrial Ca2+ overload in Drosophila versus human cells allowed us to identify a gene, MCUR1, which, when expressed in Drosophila cells, conferred permeability transition sensitive to electrophoretic Ca2+ uptake. Conversely, inhibiting MCUR1 in mammalian cells increased the Ca2+ threshold for inducing permeability transition. The effect was specific to the permeability transition induced by Ca2+, and such resistance to overload translated into improved cell survival. Thus, MCUR1 expression regulates the Ca2+ threshold required for permeability transition.

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