MICU1 occludes the mitochondrial calcium uniporter in divalent-free conditions.

Mitochondrial Ca uptake is mediated by the mitochondrial uniporter complex (mtCU) that includes a tetramer of the pore-forming subunit, MCU, a scaffold protein, EMRE, and the EF-hand regulatory subunit, MICU1 either homodimerized or heterodimerized with MICU2/3. MICU1 has been proposed to regulate Ca uptake via the mtCU by physically occluding the pore and preventing Ca flux at resting cytoplasmic [Ca] (free calcium concentration) and to increase Ca flux at high [Ca] due to cooperative activation of MICUs EF-hands. However, mtCU and MICU1 functioning when its EF-hands are unoccupied by Ca is poorly studied due to technical limitations.

Regulation of kidney mitochondrial function by caloric restriction.

Caloric restriction (CR) prevents obesity and increases resilience against pathological stimuli in laboratory rodents. At the mitochondrial level, protection promoted by CR in the brain and liver is related to higher Ca uptake rates and capacities, avoiding Ca-induced mitochondrial permeability transition. Dietary restriction has also been shown to increase kidney resistance against damaging stimuli; if these effects are related to similar mitochondrial adaptations has not been uncovered.

Mitochondrial morphology regulates organellar Ca uptake and changes cellular Ca homeostasis.

Changes in mitochondrial size and shape have been implicated in several physiologic processes, but their role in mitochondrial Ca uptake regulation and overall cellular Ca homeostasis is largely unknown. Here we show that modulating mitochondrial dynamics toward increased fusion through expression of a dominant negative (DN) form of the fission protein [dynamin-related protein 1 (DRP1)] markedly increased both mitochondrial Ca retention capacity and Ca uptake rates in permeabilized C2C12 cells. Similar results were seen using the pharmacological fusion-promoting M1 molecule.

Fasting promotes functional changes in liver mitochondria.

Overnight fasting of rodents is commonly adopted in protocols to obtain isolated liver mitochondria, but the effects of fasting itself on mitochondrial function are poorly characterized. In this study we show that overnight fasting (15 h) promotes a shift in the liver mitochondrial bioenergetic profile, with a reduction in ADP-stimulated and maximal respiration, lower membrane potentials and lower resistance to Ca-induced mitochondrial permeability transition. Short term fasting (4 h) promoted similar changes, suggesting that this is a physiological shift in mitochondrial function associated with fasting, but not torpor.

Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca-induced mitochondrial permeability transition.

Caloric restriction (CR) promotes lifespan extension and protects against many pathological conditions, including ischemia/reperfusion injury to the brain, heart and kidney. In the liver, ischemia/reperfusion damage is related to excessive mitochondrial Ca accumulation, leading to the mitochondrial permeability transition. Indeed, liver mitochondria isolated from animals maintained on CR for 4 months were protected against permeability transition and capable of taking up Ca at faster rates and in larger quantities.

Mitochondrial form, function and signalling in aging.

Aging is often accompanied by a decline in mitochondrial mass and function in different tissues. Additionally, cell resistance to stress is frequently found to be prevented by higher mitochondrial respiratory capacity. These correlations strongly suggest mitochondria are key players in aging and senescence, acting by regulating energy homeostasis, redox balance and signalling pathways central in these processes.

Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity.

Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic insults in vitro and in vivo in a manner associated with significant changes in mitochondrial function. CR increases electron transport chain activity, enhances antioxidant defenses, and favors mitochondrial calcium retention capacity in the brain.

Demethylation profile of the TNF-α promoter gene is associated with high expression of this cytokine in Dengue virus patients.

Dengue is the most prevalent arthropod-borne viral illness in humans. The overexpression of cytokines by Dengue virus (DENV) infected cells is associated with the most severe forms of the disease. Unmethylated CpG islands are related to a transcriptionally active structure, whereas methylated DNA recruits methyl-binding proteins that inhibit gene expression.