scholarly journals Calcium ion-dependent signalling and mitochondrial dysfunction: mitochondrial calcium uptake during hormonal stimulation in intact liver cells and its implication for the mitochondrial permeability transition

1995 ◽  
Vol 1271 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Jan B. Hoek ◽  
John L. Farber ◽  
Andrew P. Thomas ◽  
Xiaolan Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Calcium Ion ◽  
Calcium Uptake ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Liver Cells ◽  
Mitochondrial Calcium ◽  
Hormonal Stimulation ◽  
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 The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jasiel O. Strubbe-Rivera ◽  
Jason R. Schrad ◽  
Evgeny V. Pavlov ◽  
James F. Conway ◽  
Kristin N. Parent ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Structure And Function ◽  
Calcium Overload ◽  
Mitochondrial Permeability ◽  
Mitochondrial Structure ◽  
And Function ◽  
The Impact

AbstractMitochondria have a remarkable ability to uptake and store massive amounts of calcium. However, the consequences of massive calcium accumulation remain enigmatic. In the present study, we analyzed a series of time-course experiments to identify the sequence of events that occur in a population of guinea pig cardiac mitochondria exposed to excessive calcium overload that cause mitochondrial permeability transition (MPT). By analyzing coincident structural and functional data, we determined that excessive calcium overload is associated with large calcium phosphate granules and inner membrane fragmentation, which explains the extent of mitochondrial dysfunction. This data also reveals a novel mechanism for cyclosporin A, an inhibitor of MPT, in which it preserves cristae despite the presence of massive calcium phosphate granules in the matrix. Overall, these findings establish a mechanism of calcium-induced mitochondrial dysfunction and the impact of calcium regulation on mitochondrial structure and function.

Mitochondrial Permeability Transition Pore Sealing Agents and Antioxidants Protect Oxidative Stress and Mitochondrial Dysfunction Induced by Naproxen, Diclofenac and Celecoxib

Drug Research ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 598-605 ◽  
Author(s):  
Ahmad Salimi ◽  
Mohammad Reza Neshat ◽  
Parvaneh Naserzadeh ◽  
Jalal Pourahmad
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Isolated Rat Heart ◽  
Atp Depletion ◽  
Mitochondrial Permeability ◽  
Pore Sealing ◽  
Increased Risk

AbstractNonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen, diclofenac and celecoxib used to reduce pain. Many of these drugs have been associated with an increased risk of cardiovascular disease (CVD). The molecular mechanism(s) by which NSAIDs induce CVD up to now is unknown. We investigated the effects of naproxen, diclofenac and celecoxib with different structures and mechanism action on isolated rat heart mitochondria. All tested NSAIDs increased reactive oxygen species (ROS) formation, mitochondrial membrane collapse (MMP), mitochondrial swelling, lipid peroxidation, and glutathione and ATP depletion, which all of them play important roles in developing cardiotoxicity. We reported that mitochondrial permeability transition (MPT) pore sealing agents and antioxidants have the capacity to significantly prevent mitochondrial toxicity. Therefore, the inhibition of mitochondrial oxidative stress and mitochondrial dysfunction by MPT pore sealing agents and antioxidants can double confirm NSAID-induced cardiomyocytes toxicity is resulted from induction of apoptosis signaling trough ROS-mediated mitochondrial permeability transition.

scholarly journals Mitochondrial Permeability Transition: A Pore Intertwines Brain Aging and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 649
Author(s):  
Kun Jia ◽  
Heng Du
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Brain Aging ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Disorders ◽  
Mitochondrial Permeability

Advanced age is the greatest risk factor for aging-related brain disorders including Alzheimer’s disease (AD). However, the detailed mechanisms that mechanistically link aging and AD remain elusive. In recent years, a mitochondrial hypothesis of brain aging and AD has been accentuated. Mitochondrial permeability transition pore (mPTP) is a mitochondrial response to intramitochondrial and intracellular stresses. mPTP overactivation has been implicated in mitochondrial dysfunction in aging and AD brains. This review summarizes the up-to-date progress in the study of mPTP in aging and AD and attempts to establish a link between brain aging and AD from a perspective of mPTP-mediated mitochondrial dysfunction.

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