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1.
Ca2+ stimulates the binding of a variety of prostaglandins (PG) to liver mitochondria. Optimal binding is observed at slightly acidic pH and at concentrations of Ca2+ between 200 and 500 μm. The stimulation of the binding requires the active transport of Ca2+ in mitochondria and is only observed in the absence of permeant anions. The maximal amount of PG bound is about 3 nmol/mg of mitochondrial protein. All PG tested induce efflux of the Ca2+ taken up by mitochondria without impairing the ability of mitochondria to actively accumulate it. Optimal stimulation of the efflux of Ca2+ requires concentrations of PG higher than those used in the PG-binding experiments and is associated with an evident uncoupling of the respiration that follows a Ca2+-induced O2 uptake jump. The “uncoupling” by PG is explained by postulating the entrance of protonated PG into mitochondria, followed by their exit from the organelle as 2:1 complexes with Ca2+.  相似文献   

2.
A hydrophobic, low-molecular weight component extracted from mitochondria forms aCa2+-activated ion channel in black-lipid membranes (Mironova et al., 1997). At pH 8.3–8.5, thecomponent has a high-affinity binding site for Ca2+ with a Kd of 8 × 10–6 M, while at pH7.5 this Kd was decreased to 9 × 10–5 M. Bmax for the Ca2+-binding site did not changesignificantly with pH. In the range studied, 0.2 ± 0.06 mmol Ca2+/g component were boundor one calcium ion to eight molecules of the component. The Ca2+ binding was stronglydecreased by 50–100 mM Na+, but not by K+. Treatment of mitochondria withCaCl2 priorto ethanolic extraction resulted in a high level of Ca2+-binding capacity of the partially purifiedcomponent. Cyclosporin A, a specific inhibitor of the mitochondrial permeability transition,when added to the mitochondrial suspension, decreased the Ca2+-binding activity of thepurified extract severalfold. The calcium-binding capability of the partially purified componentcorrelates with its calcium-channel activity. This indicates that the channel-forming componentmight be involved in the permeability transition that stimulates its formation.  相似文献   

3.
Abstract: Neuroblastoma × glioma hybrid cells increase their intracellular concentration of cyclic AMP in response to prostaglandin E1 (PGE1). This effect is inhibited by opioids. The response to PGE1 is positively correlated with the concentration of Ca2+ in the incubation medium. The Ca2+ antagonists Co2+ and La3+, the Ca2+ chelator EGTA and a blocker of Ca2+ influx into cells, Segontin, inhibit the response to PGE1. At low external concentrations of Ca2+ the response to PGE1 is enhanced by the Ca2+ ionophore A23187. The effects of A23187 and Segontin point to a cytosolic site of Ca2+ action. Lack of Ca2+ reduces the level of cyclic AMP even in the absence of PGE1 and the presence of an inhibitor of cyclic AMP phosphodiesterase. Ca2+ is required even for an increase in the level of cyclic AMP in cells pretreated with cholera toxin. The increases in level of cyclic AMP evoked by PGE, in a neuroblastoma and by PGE1 or noradrenaline in a glioma cell line do not depend on Ca2+. The response of the hybrid cells to the opioid leucine-enkephalin appears not to rely on the presence of Ca2+. Even changing the intracellular concentration of Ca2+ by the ionophore A23187 does not alter the effect of the opioid. The analogy between opioids and lack of Ca2+ in the short-term (minutes) experiments mentioned holds also for long-term (hours) experiments. Cells chronically exposed to opioids or to low concentrations of Ca2+ display an enhanced maximal response to PGE1.  相似文献   

4.
Chlorotetracycline inhibits the uncoupled oxidation of exogenous NADH by Jerusalem artichoke (Helianthus tuberosus L.) mitochondria extensively (over 80%) and rapidly (inhibition complete in 10 s) in the presence of added Ca2+. Half-maximal inhibition is observed at 15 μM chlorotetracycline in the presence of 2 mM Ca2+. The oxidation of succinate is only affected marginally by chlorotetracycline plus Ca2+. The inhibition of NADH oxidation and the fluorescence of CTC are well correlated. Mn2+ is the only other cation which shows an (increased) inhibition in the presence of chlorotetracycline. The inhibition by Ca2+ and chlorotetracycline disappears at acid pH, and the pH optimum in their presence is 6.4. The inhibition caused by other lipid-soluble Ca2+-chelators is not reversible or is enhanced by the addition of excess Ca2+. In contrast, inhibition caused by relatively water-soluble chelators is completely reversed by added Ca2+. It is suggested that a neutral 1:2 complex is formed between Ca2+ and chlorotetracycline which can substitute for Ca2+ bound at sites in the lipophilic phase of the inner mitochondrial membrane, which are essential for the activity of the external NADH dehydrogenase.  相似文献   

5.
The kinetic plot (initial rate of Ca2+ transport versus concentration) of mitochondrial Ca2+ transport is hyperbolic in a sucrose medium. The plot becomes sigmoidal in the presence of competitive inhibitors of Ca2+ binding to low affinity sites of the membrane surface such as Mg2+ and K+. The plot also becomes sigmoidal in the presence of Ba2+. Ba2+ is a competitive inhibitor of both Ca2+ transport and Ca2+ binding to the low affinity sites. The Ki for the inhibition of Ca2+ transport by Ba2+ increases in the presence of K+ and Mg2+, which suggests a competition for the low affinity sites between the cations. The plot is still hyperbolic in the presence of La3+, which inhibits Ca2+ transport competitively. Ruthenium red which is a pure non-competitive inhibitor of mitochondrial Ca2+ transport, does not affect the shape of the kinetic plot. These results indicate that the surface potential, which depends on the ions bound to the low affinity sites, determines whether the kinetics of Ca2+ uptake in mitochondria is sigmoidal or hyperbolic.  相似文献   

6.
La3+ inhibits the respiration-dependent accumulation of Ca2+ by rat liver mitochondria when added in very small amounts (0.1–l.0 nmole per mg protein). However, La3+ itself does not activate respiration. With the use of 140La3+ it was found that La3+ is very rapidly bound to rat liver mitochondria in a respiration-independent process accompanied by loss of H+ to the medium. When both La3+ and Ca2+ are added to mitochondria simultaneously, most of the La3+ but little Ca2+ are bound. La3+ added to mitochondria previously loaded with Ca2+ is tightly bound without discharge of Ca2+. Conversely, when Ca2+ is added to La3+-loaded mitochondria it is not bound nor is the La3+ discharged. La3+ inhibits both high-affinity and low-affinity respiration-independent Ca2+ binding. Isotopic experiments showed that La3+ is, in fact, bound to the same high-affinity sites as Ca2+, in both intact mitochondria and in mitochondrial extracts. It is concluded (1) that La3+ binds to and inhibits the Ca2+ carrier; (2) that La3+ is not transported by the Ca2+ carrier; and (3) that La3+ is, in addition, bound to a large number of external sites on mitochondria for which Ca2+ is not a strong competitor.  相似文献   

7.
Summary Under physiological conditions cardiac mitochondria seem to play a minor role in maintaining intracellular Ca2+ homoeostasis. However, under conditions of cellular Ca2+ overload, mitochondria may accumulate large amounts of Ca2+. Using transmission and analytical electron microscopy we investigated, in globally ischaemic rat heart preparations, the influence of intracellular pH on the development of Ca2+-containing intramitochondrial inclusions. We confirmed that under these experimental conditions Ca2+ was a major element of mitochondrial inclusions. The size of these inclusions increased with external Ca2+ concentration. An intracellular alkalinization, produced by addition of 20mm NH4Cl to the perfusate prior to ischaemia, inhibited the formation of such inclusions. On the other hand, a pre-ischaemic intracellular acidification, produced by the addition and subsequent withdrawal of the 20mm NH4Cl, increased the number of inclusions present at the end of an ischaemic episode. The presence of amiloride (10–3 m), prior to and during ischaemia, increased the number of inclusions. These data suggest that cytoplasmic pH may be an important factor in mitochondrial Ca2+ accumulation in pathological conditions.  相似文献   

8.
Anticoagulation factor I (ACF I) from the venom of Agkistrodon acutus forms a 1:1 complex with activated coagulation factor X (FXa) in a Ca2+-dependent fashion and thereby prolongs the clotting time. In the present study, the dependence of the binding of ACF I with FXa on the concentration of Ca2+ ions was quantitatively analyzed by HPLC, and the result showed that the maximal binding of ACF I to FXa occurred at concentration of Ca2+ ions of about 1 mM. The binding of Ca2+ ions to ACF I was investigated by equilibrium dialysis and two Ca2+-binding sites with different affinities were identified. At pH 7.6, the apparent association constants K1 and K2 for these two sites were (1.8 ± 0.5) × 105 and (2.7 ± 0.6) × 104 M–1 (mean ± SE, n = 4), respectively. It was evident from the observation of Ca2+-induced changes in the intrinsic fluorescence of ACF I that ACF I underwent a conformational change upon binding of Ca2+ ions. The occupation of both Ca2+-binding sites in ACF I required a concentration of Ca2+ ions of about 1 mM, which is equal to the effective concentration of Ca2+ ions required both for maximal binding of ACF I to FXa and for the maximal enhancement of emission fluorescence of ACF I. It could be deduced from these results that the occupation of both Ca2+-binding sites in ACF I with Ca2+ ions and subsequent conformational rearrangement might be essential for the binding of ACF I to FXa.  相似文献   

9.
Despite extensive research, the regulation of mitochondrial function is still not understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic task in co-ordinating the cellular work load and the regeneration of ATP by mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by the supply of glutamate to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier. Since this activation is not affected by ruthenium red, glutamate transport into mitochondria is controlled exclusively by extramitochondrial Ca2+. Therefore, this discovery shows that besides intramitochondrial also extramitochondrial Ca2+ regulates oxidative phosphorylation. This new mechanism acts as a mitochondrial “gas pedal”, supplying the OXPHOS with substrate on demand. These results are in line with recent findings of Satrustegui and Palmieri showing that aralar as part of the malate–aspartate shuttle is involved in the Ca2+-dependent transport of reducing hydrogen equivalents (from NADH) into mitochondria. This review summarises results and evidence as well as hypothetical interpretations of data supporting the view that at the surface of mitochondria different regulatory Ca2+-binding sites exist and can contribute to cellular energy homeostasis. Moreover, on the basis of our own data, we propose that these surface Ca2+-binding sites may act as targets for neurotoxic proteins such as mutated huntingtin and others. The binding of these proteins to Ca2+-binding sites can impair the regulation by Ca2+, causing energetic depression and neurodegeneration.  相似文献   

10.
Under high Ca2+ load conditions, Ca2+ concentrations in the extra-mitochondrial and mitochondrial compartments do not display reciprocal dynamics. This is due to a paradoxical increase in the mitochondrial Ca2+ buffering power as the Ca2+ load increases. Here we develop and characterize a mechanism of the mitochondrial Ca2+ sequestration system using an experimental data set from isolated guinea pig cardiac mitochondria. The proposed mechanism elucidates this phenomenon and others in a mathematical framework and is integrated into a previously corroborated model of oxidative phosphorylation including the Na+/Ca2+ cycle. The integrated model reproduces the Ca2+ dynamics observed in both compartments of the isolated mitochondria respiring on pyruvate after a bolus of CaCl2 followed by ruthenium red and a bolus of NaCl. The model reveals why changes in mitochondrial Ca2+ concentration of Ca2+ loaded mitochondria appear significantly mitigated relative to the corresponding extra-mitochondrial Ca2+ concentration changes after Ca2+ efflux is initiated. The integrated model was corroborated by simulating the set-point phenomenon. The computational results support the conclusion that the Ca2+ sequestration system is composed of at least two classes of Ca2+ buffers. The first class represents prototypical Ca2+ buffering, and the second class encompasses the complex binding events associated with the formation of amorphous calcium phosphate. With the Ca2+ sequestration system in mitochondria more precisely defined, computer simulations can aid in the development of innovative therapeutics aimed at addressing the myriad of complications that arise due to mitochondrial Ca2+ overload.  相似文献   

11.
NADPH is a key reductant carrier that maintains internal redox and antioxidant status, and that links biosynthetic, catabolic and signalling pathways. Plants have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and pH in vitro, but concentrations of Ca2+ needed are not known. We have determined the K0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over the physiological pH range using O2 and decylubiquinone as electron acceptors. The K0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation, and unlike the latter, it depended on pH. At pH 7.5, K0.5(Ca2+) for NADPH oxidation was high (≈100 μM), yet 20-fold lower K0.5(Ca2+) values were determined at pH 6.8. Lower K0.5(Ca2+) values were observed with decylubiquinone than with O2 as terminal electron acceptor. NADPH oxidation responded to changes in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic acidification is an important activator of external NADPH oxidation, by decreasing the Ca2+-requirements for NDB1. The results are discussed in relation to the present knowledge on how whole cell NADPH redox homeostasis is affected in plants modified for the NDB1 gene.  相似文献   

12.
THE energy-dependent accumulation of Ca2+ by isolated rat liver mitochondria is intimately associated with oxidative phosphorylation1. Available evidence supports the idea that, like the permeases postulated for some mitochondrial metabolites2, this active accumulation of Ca2+ may involve a “carrier” in the mitochondrial membrane specific for Ca2+ (ref. 3). Several studies have shown that the energy-independent “binding” of Ca2+ to sites on the (inner membrane of), intact mitochondria and of submitochondrial particles exhibits hyperbolic saturation curves as a function of Ca2+ concentration4, 5.  相似文献   

13.
ATP-dependent Ca2+ uptake distinct from that of the mitochondria is found in both plasma membrane and microsomal membranes of rat kidney. Activity attributed to these fractions is enhanced by ammonium oxalate and is apparently insensitive to NaN3. In contrast, rat kidney mitochondrial Ca2+ uptake is blocked by NaN3. The pH of optimal activity is significantly higher for the mitochondrial fraction. Microsomal membrane Ca2+ uptake differs from that of the plasma membrane. Microsomal membranes are four times as active as the plasma membrane at high (5 mM) ATP levels. Apparent Km values for Mg2+-ATP differ in the two preparations with a higher affinity for Mg2+-ATP found in the plasma membrane Ca2+ uptake activity of the plasma membrane preparation is readily inhibited by Na+. Sucrose gradient density fractionation indicates that the observed microsomal membrane Ca2+ pump activity is associated with membrane vesicles derived from the endoplasmic reticulum. Ca2+ pump activity of both plasma membrane and microsomal fraction is depressed din the adrenalectomized rat. This activity is not restored by a single natriuretic dose of aldosterone.  相似文献   

14.
The effects of hydrophobic and hydrophilic bile acids as inducers of Ca2+-dependent permeability of the inner membrane were studied on isolated liver mitochondria. It is shown that in the absence of the inorganic phosphate (Pi)–a modulator of the mitochondrial pore–hydrophobic bile acids (lithocholic, deoxycholic, chenodeoxycholic) at concentrations of 20–50 μM, as well as a hydrophilic cholic acid at a concentration of 800 μM, induce swelling of liver mitochondria loaded with Ca2+. This effect is completely eliminated by a specific inhibitor of mitochondrial pore cyclosporin A (CsA). The effect of the bile acids as inducers of Ca2+-dependent CsA-sensitive mitochondrial pore is not associated with the modulation of the Pi effects. In contrast to other tested bile acids, a hydrophilic ursodeoxycholic acid (UDCA) at a concentration of 400 μM is able to induce Ca2+-dependent CsA-sensitive pore opening in liver mitochondria only in the presence of Pi or in the absence of potassium chloride in the incubation medium. In the presence of potassium chloride but in the absence of Pi, UDCA effects associated with the induction of the inner membrane permeability (swelling of mitochondria, drop in Δψ, and Ca2+ release from the matrix) are also observed in the presence of CsA. This Ca2+-dependent permeability of the inner membrane, in contrast to the “classical” CsA-sensitive pore, is characterized by a lower intensity of the mitochondrial swelling, a total drop in Δψ, and Ca2+ release from the matrix and is blocked by Pi. We suggest that the induction of the CsA-insensitive permeability in the inner mitochondrial membrane by UDCA is associated with activation of electrophoretic influx of K+ into the matrix and Ca2+ release from the matrix in exchange to H+. The effect of Pi as a blocker of such permeability is discussed.  相似文献   

15.
The amination of α-ketoglutarate (α-KG) by NADH-glutamate dehydrogenase (GDH) obtained from Sephadex G-75 treated crude extracts from shoots of 5-day-old seedlings was stimulated by the addition of Ca2+. The NADH-GDH purified 161-fold with ammonium sulfate, DEAE-Toyopearl, and Sephadex G-200 was also activated by Ca2+ in the presence of 160 micromolar NADH. However, with 10 micromolar NADH, Ca2+ had no effect on the NADH-GDH activity. The deamination reaction (NAD-GDH) was not influenced by the addition of Ca2+.

About 25% of the NADH-GDH activity was solubilized from purified mitochondria after a simple osmotic shock treatment, whereas the remaining 75% of the activity was associated with the mitochondrial membrane fraction. When the lysed mitochondria, mitochondrial matrix, or mitochondrial membrane fraction was used as the source of NADH-GDH, Ca2+ had little effect on its activity. The mitochondrial fraction contained about 155 nanomoles Ca per milligram of mitochondrial protein, suggesting that the NADH-GDH in the mitochondria is already in an activated form with regard Ca2+. In a simulated in vitro system using concentrations of 6.4 millimolar NAD, 0.21 millimolar NADH, 5 millimolar α-KG, and 5 millimolar glutamate thought to occur in the mitochondria, together with 1 millimolar Ca2+, 10 and 50 millimolar NH4+, and purified enzyme, the equilibrium of GDH was in the direction of glutamate formation.

  相似文献   

16.
Intracellular Ca2+ ([Ca2+]i) dynamics were studied in identified rat gonadotropes using the whole-cell patch-clamp technique in conjunction with Indo-1 photometry. The kinetics of depolarization-induced [Ca2+]i transients vary with Ca2+ load. In addition to a rapid initial decay, large (> 500 nM) [Ca2+]i transients have a slow plateau phase. Application of the mitochondrial inhibitor carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly slows the decay of [Ca2+]i transients, consistent with stopping uptake of Ca2+ by mitochondria. CCCP causes a small increase of [Ca2+]i at rest. After a large Ca2+ entry the amount is much larger, consistent with release from a mitochondrial Ca2+ pool that fills during cytoplasmic Ca2+ loading. The rate of Ca2+ uptake by mitochondria is dependent upon [Ca 2+]i. Consistent with previous studies, gonadotropin releasing hormone (GnRH) induces [Ca2+]i oscillations. The mitochondrial inhibitors CCCP and cyanide (CN) terminate these oscillations. The mitochondrial ATP-synthase inhibitor oligomycin reduces the frequency and increases the amplitude of the oscillations. In the presence of ruthenium red (a non-specific blocker of the mitochondrial Ca2+-uniporter) in the pipette, GnRH does not induce rhythmic [Ca2+]i oscillations. We suggest that mitochondria play a significant role in the rapid clearance of cytosolic Ca2+ loads in gonadotropes and participate in GnRH-induced periodic [Ca2+]i oscillations.  相似文献   

17.
  1. The affinity of ATP-supported Ca2+ accumulation for both Ca2+ and ATP was determined from initial rate studies employing isolated rat liver mitochondria. TheK m values for “free” Ca2+ and ATP were calculated to be of the order of 2 μM and 100 μM, respectively. TheK m for ATP decreased as the Ca2+ concentration was increased.
  2. The curve relating initial rates of Ca2+ accumulation to Ca2+ concentration was singmoidal in shape; values obtained for the Hill coefficient were in the range 1.5–1.9.
  3. Concomitant with the ATP-stimulated accumulation of Ca2+, ATP translocation was itselt increased in the presence of Ca2+. This stimulation took place independently of Ca2+ accumulation.
  4. Decreasing the pH of the incubation medium decreased the rate of Ca2+ accumulation. This inhibition was competitive in that the affinity of mitochondrial for Ca2+ could be altered. The maximal rate of accumulation did not change with change in pH.
  5. The permeant anions inorganic phosphate and acetate stimulated the accumulation of Ca2+ in a non-competitive manner. Both theV max and Km varied when either of the anions were present.
  6. The data are discussed in relation to the role that mitochondria play in controlling the cellular ionic environment.
  相似文献   

18.
In order to explore the role of mitochondria in proliferation promotion and/or apoptosis induction of lanthanum, the mutual influences between La3+ and Ca2+ on mitochondrial permeability transition pore (PTP) opening were investigated with isolated mitochondria from rat liver. The experimental results revealed that La3+ influence the state of mitochondria in a concentration-dependent biphasic manner. La3+ in nanomolar concentrations, acting as a Ca2+ analog, entered mitochondrial matrix via the RuR sensitive Ca2+ channel and elevated ROS level, leading to opening of PTP indicated by mitochondrial swelling, reduction of ΔΨm and cytochrome c release. Inhibition of PTP with 10 μM CsA attenuated the effects of La3+. However, micromolar concentrations La3+ acted mainly as a Ca2+ antagonist, inhibiting PTP opening induced by Ca2+. We postulated that this action of La3+ on mitochondria through interaction with Ca2+ might be involved in the proliferation-promoting and apoptosis induction by La3+.  相似文献   

19.
Excessive Ca2+ fluxes from the endoplasmic reticulum to the mitochondria result in apoptotic cell death. Bcl-2 and Bcl-XL proteins exert part of their anti-apoptotic function by directly targeting Ca2+-transport systems, like the endoplasmic reticulum-localized inositol 1,4,5-trisphosphate receptors (IP3Rs) and the voltage-dependent anion channel 1 (VDAC1) at the outer mitochondrial membranes. We previously demonstrated that the Bcl-2 homology 4 (BH4) domain of Bcl-2 protects against Ca2+-dependent apoptosis by binding and inhibiting IP3Rs, although the BH4 domain of Bcl-XL was protective independently of binding IP3Rs. Here, we report that in contrast to the BH4 domain of Bcl-2, the BH4 domain of Bcl-XL binds and inhibits VDAC1. In intact cells, delivery of the BH4-Bcl-XL peptide via electroporation limits agonist-induced mitochondrial Ca2+ uptake and protects against staurosporine-induced apoptosis, in line with the results obtained with VDAC1−/− cells. Moreover, the delivery of the N-terminal domain of VDAC1 as a synthetic peptide (VDAC1-NP) abolishes the ability of BH4-Bcl-XL to suppress mitochondrial Ca2+ uptake and to protect against apoptosis. Importantly, VDAC1-NP did not affect the ability of BH4-Bcl-2 to suppress agonist-induced Ca2+ release in the cytosol or to prevent apoptosis, as done instead by an IP3R-derived peptide. In conclusion, our data indicate that the BH4 domain of Bcl-XL, but not that of Bcl-2, selectively targets VDAC1 and inhibits apoptosis by decreasing VDAC1-mediated Ca2+ uptake into the mitochondria.  相似文献   

20.
Leucine Zipper EF‐hand containing transmembrane protein‐1 (LETM1) is an inner mitochondrial membrane protein that mediates mitochondrial calcium (Ca2+)/proton exchange. The matrix residing carboxyl (C)‐terminal domain contains a sequence identifiable EF‐hand motif (EF1) that is highly conserved among orthologues. Deletion of EF1 abrogates LETM1 mediated mitochondrial Ca2+ flux, highlighting the requirement of EF1 for LETM1 function. To understand the mechanistic role of this EF‐hand in LETM1 function, we characterized the biophysical properties of EF1 in isolation. Our data show that EF1 exhibits α‐helical secondary structure that is augmented in the presence of Ca2+. Unexpectedly, EF1 features a weak (~mM), but specific, apparent Ca2+‐binding affinity, consistent with the canonical Ca2+ coordination geometry, suggested by our solution NMR. The low affinity is, at least in part, due to an Asp at position 12 of the binding loop, where mutation to Glu increases the affinity by ~4‐fold. Further, the binding affinity is sensitive to pH changes within the physiological range experienced by mitochondria. Remarkably, EF1 unfolds at high and low temperatures. Despite these unique EF‐hand properties, Ca2+ binding increases the exposure of hydrophobic regions, typical of EF‐hands; however, this Ca2+‐induced conformational change shifts EF1 from a monomer to higher order oligomers. Finally, we showed that a second, putative EF‐hand within LETM1 is unreactive to Ca2+ either in isolation or tandem with EF1. Collectively, our data reveal that EF1 is structurally and biophysically responsive to pH, Ca2+ and temperature, suggesting a role as a multipartite environmental sensor within LETM1.  相似文献   

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