Adenine nucleotide content of liver mitochondria increases after glucagon treatment of rats or isolated hepatocytes

Aprille, June R.; Nosek, Michael T.; Brennan, William A.

doi:10.1016/0006-291x(82)90905-6

Cited by 26 publications

(11 citation statements)

References 12 publications

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“…Firstly, PP1 is known to be a substrate with a low affinity for the adenine nucleotide translocator (Kramer, 1980;Asimakis & Aprille, 1980;D'Souza & Wilson, 1982) and, as outlined above, this translocator has been implicated in the increase in matrix volume induced by Ca2l. Secondly, it has been observed in several laboratories that the total adenine nucleotide content of liver mitochondria increases after hormone treatment (Bryla et al, 1977;Siess et al, 1977;Titheradge & Haynes, 1980;Aprille et al, 1982;Soboll & Scholz, 1986). Since PP1 can exchange with adenine nucleotides on the ATP/ADP translocator, this observation would be consistent with a rise in mitochondrial [PPJ in response to hormones under the conditions known to cause an increase in mitochondrial matrix volume (Quinlan et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

Davidson

Halestrap

1987

Biochemical Journal

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1. The matrix pyrophosphate (PPi) content of isolated energized rat liver mitochondria incubated in the presence of ATP, Mg2+, Pi and respiratory substrate was about 100 pmol/mg of protein. 2. After incubation with sub-micromolar [Ca2+], this was increased by as much as 300%. There was a correlation between the effects of Ca2+ on PPi and on the increase in matrix volume reported previously [Halestrap, Quinlan, Whipps & Armston (1986) Biochem. J. 236, 779-787]. Half-maximal effects were seen at 0.3 microM-Ca2+. 3. Coincident with these effects, the total adenine nucleotide content increased in a carboxyatractyloside-sensitive manner. 4. Incubation with 0.2-0.5 mM-butyrate induced similar but smaller effects on mitochondrial swelling and matrix PPi and total adenine nucleotide content. Addition of butyrate after Ca2+, or vice versa, caused Ca2+-induced mitochondrial swelling to stop or reverse, while matrix PPi increased 30-fold. 5. Addition of atractyloside or the omission of ATP from incubations greatly enhanced swelling induced by Ca2+ without increasing matrix PPi. 6. Swelling of mitochondria incubated under de-energized conditions in iso-osmotic KSCN was progressively enhanced by the addition of increasing concentrations of PPi (1-20 mM) or valinomycin. 7. In iso-osmotic potassium pyrophosphate swelling was slow initially, but accelerated with time. This acceleration was inhibited by ADP, whereas carboxyatractyloside induced rapid swelling. Swelling in other iso-osmotic PPi salts showed that the rate of entry decreased in the order NH4+ greater than K+ greater than Na+ greater than Li+, whereas choline, tetramethylammonium and Tris did not enter. It is suggested that the adenine nucleotide translocase transports small univalent cations when PPi is bound and that PPi can also be transported when the transporter is in the conformation induced by carboxyatractyloside. 8. It is concluded that Ca2+ and butyrate cause swelling of energized mitochondria through this effect of PPi on K+ permeability of the mitochondrial inner membrane. 9. Freeze-clamped livers from rats treated with glucagon or phenylephrine show 30-50% increases in tissue PPi. It is proposed that Ca2+-mediated increases in mitochondrial PPi are responsible for the increase in matrix volume and total adenine nucleotide content observed after hormone treatment.

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Section: Introductionmentioning

confidence: 99%

Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

Davidson

Halestrap

1987

Biochemical Journal

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“…Insulin inhibits and glucagon stimulates mitochondrial adenine nucleotide accumulation in full-term newborn rabbits (9) (Tullson PC, Aprille JR, unpublished data). The insulin/glucagon ratio influences the adenine nucleotide pool size in adult rat liver mitochondria also (28)(29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hypoxia or Maternal Diabetes Delays Postnatal Development of Liver Mitochondria

Aprille

Nosek

1987

Pediatr Res

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ABSTRACT. The matrix adenine nucleotide pool size of rat liver mitochondria was low at birth (2.6-3.0 nmol ATP+ADP+AMP/mg mitochondrial protein). After parturition, the pool size was increased by 50-75% within 1 h, which was sufficient for full development of state 3 respiration rates. The adenine nucleotide pool size continued to increase to 100-150% of the value at birth by 2-3 h postnatal. The ATPIADP ratio in isolated mitochondria also increased postnatally, to about double the value at birth by 3 h. There were no matrix volume changes over this postnatal period, so the increased ATP+ADP+AMP pool size and the increased ATPIADP ratio together inferred an overall increase of about 5-fold in the matrix ATP concentration under aerobic conditions. The postnatal uptake of adenine nucleotides into mitochondria occurred at a slower rate in newborns that were hypoxic (11% Oz) and in newborns of diabetic mothers (diabetes induced on day 5 of gestation by streptozotocin injection). The normal increase in matrix ATP content is responsible for the rapid stimulation of pyruvate carboxylation (an ATP-requiring matrix reaction) and this in turn contributes to the rapid postnatal onset of gluconeogenesis. The results suggest that delayed adenine nucleotide uptake into liver mitochondria may retard initiation of gluconeogenesis in newborns experiencing hypoxia, as in respiratory distress or in newborns of diabetic mothers. We speculate that this mechanism contributes to the persistent hypoglycemia that is typical of these at-risk newborns. (Pediatr Res 21: 266-269,1987) Mitochondria isolated from full-term fetal rat liver are functionally well coupled, but the rate of oxidative phosphorylation (state 3 respiration) is very low (reviewed in Reference 1). Within 1 h after birth, the state 3 rate increases to adult values (2-4). This functional maturation depends on a rapid increase in the mitochondrial adenine nucleotide content (ATP+ADP+AMP) which occurs in the immediate postnatal period (2, 4-6) In addition to activating state 3 respiration the increased adenine nucleotide pool size may also stimulate metabolic pathways that have adenine nucleotide-dependent enzymes within the mitochondrial compartment (reviewed in Reference 1). One matrix enzyme subject to this kind of control is pyruvate carboxylase. In both the newborn rat and rabbit the sudden postnatal increase in the matrix ATP concentration enhances pyruvate carboxylation rates enabling the onset of gluconeogenesis and recovery from postnatal hypoglycemia (7-9). Thus, the accumulation of adenine nucleotides into the mitochondria appears to be important for metabolic adaptation to neonatal life (see Reference 1).Received May 13, 1986; accepted October 23, 1986. Correspondence and reprint requests Dr. June R. Aprille, Mitochondria1 Physiology Unit, Department of Biology, Tufts University, Medford, MA 02155.Supported by NIH Grants HD 16936 and NS 14936.There is considerable evidence that hormones and oxygenation are important controlling factors for the subcellular red...

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“…During fasting, glucagon secreted by ␣-cells in the pancreas activates a complex metabolic response in liver cells that includes glycogen breakdown, gluconeogenesis, urea synthesis, uptake of adenine nucleotides (AdNs), 5 and increase in the Ca 2ϩ retention capacity (CRC) of the mitochondria, and stimulation of oxidative phosphorylation (OXPHOS) (1,2). Although the primary pathway of glucagon action involves binding of the hormone to a G-protein-coupled receptor and formation of cAMP through activation of adenylate cyclase, a cytosolic Ca 2ϩ signal is also produced both by release of intra-cellular stores and Ca 2ϩ entry in the cell (3).…”

Section: It Has Been Known For a Long Time That Mitochondria Isolatedmentioning

confidence: 99%

“…SCaMC-3 is able to induce an increase in liver mitochondrial AdN content and coupled respiration that does not occur in SCaMC-3-KO mitochondria, we next studied whether this mechanism is responsible for glucagon stimulation of mitochondrial respiration in hepatocytes (2). The stimulation by glucagon of AdN uptake in liver mitochondria is dependent on the generation of a Ca 2ϩ signal (4).…”

Section: Glucagon and Phenylephrine Exert Their Effects On Mitochondrmentioning

confidence: 99%

Glucagon Regulation of Oxidative Phosphorylation Requires an Increase in Matrix Adenine Nucleotide Content through Ca2+ Activation of the Mitochondrial ATP-Mg/Pi Carrier SCaMC-3

Amigo

Traba

Barroso

et al. 2013

Journal of Biological Chemistry

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Background: Glucagon stimulates liver respiration. Results: SCaMC-3 is the only functional mitochondrial ATP-Mg/P i carrier in adult liver and SCaMC-3 deficiency prevents glucagon effects in hepatocytes and in vivo. Conclusion: SCaMC-3 is required for the stimulation of oxidative phosphorylation in response to glucagon through a Ca 2ϩ -dependent increase of mitochondrial adenine nucleotides and Ca 2ϩ retention. Significance: Ca 2ϩ stimulation of SCaMC-3 is required for liver response to glucagon.

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Adenine nucleotide content of liver mitochondria increases after glucagon treatment of rats or isolated hepatocytes

Cited by 26 publications

References 12 publications

Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

Neonatal Hypoxia or Maternal Diabetes Delays Postnatal Development of Liver Mitochondria

Glucagon Regulation of Oxidative Phosphorylation Requires an Increase in Matrix Adenine Nucleotide Content through Ca2+ Activation of the Mitochondrial ATP-Mg/Pi Carrier SCaMC-3

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