Effects of Zn2+ on the Activity and Binding of the Mitochondrial ATPase Inhibitor Protein, IF1

Overview

Journal J Bioenerg Biomembr

Publisher Springer

Specialties Biochemistry
Biology
Endocrinology

Date 1993 Jun 1

PMID 8349574

Citations 1

Authors

W Rouslin

C W Broge

B V Chernyak

Affiliations

Soon will be listed here.

Abstract

Zn2+ caused a noninhibitory binding of IF1 to mitochondrial membranes in both rabbit heart SMP and intact rabbit heart mitochondria. This Zn(2+)-induced IF1 binding required the presence of at least trace amounts of MgATP and was essentially independent of pH between 6.2 and 8.2. Addition of Zn2+ after the formation of fully inhibited IF1-ATPase complexes very slowly reversed IF1-mediated ATPase inhibition without causing significant IF1 release from the membranes. When Zn2+ was added during the state 4 energization of ischemic mitochondria in which IF1 was already functionally bound, it slowed somewhat energy-driven ATPase activation. This slowing was probably due to the fairly large depressing effect Zn2+ had upon membrane potential development, but Zn2+ did not decrease the degree of ATPase activation eventually reached at 20 min of state 4 incubation. Zn2+ also preempted normal IF1 release from the membranes, causing what little inhibitor that was released to rebind to the enzyme in noninhibitory IF1-ATPase complexes. The data suggest that IF1 can interact with the ATPase in two ways of through two kinds of sites: (a) a noninhibitory interaction involving a non-inhibitory IF1 conformation and/or an IF1 docking site on the enzyme and (b) an inhibitory interaction involving an inhibitory IF1 conformation and/or a distinct ATPase activity regulatory site. Zn2+ appears to have the dual effect of stabilizing the noninhibitory IF1-ATPase interaction and possibly a noninhibitory IF1 conformation while concomitantly preventing the formation of an inhibitory IF1-ATPase interaction and possibly an inhibitory IF1 conformation, regardless of pH. While the data do not rule out direct effects of Zn2+ on either free IF1 or the free enzyme, they suggest that Zn2+ cannot interact readily with either the inhibitor or the enzyme once functional IF1-ATPase complexes are formed.

Citing Articles

Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems.

Lee S Oxid Med Cell Longev. 2018; 2018:9156285.

PMID: 29743987 PMC: 5884210. DOI: 10.1155/2018/9156285.

References

Akerman K, Wikstrom M . Safranine as a probe of the mitochondrial membrane potential. FEBS Lett. 1976; 68(2):191-7. DOI: 10.1016/0014-5793(76)80434-6. View

Rouslin W . Factors affecting the loss of mitochondrial function during zero-flow ischemia (autolysis) in slow and fast heart-rate hearts. J Mol Cell Cardiol. 1988; 20(11):999-1007. DOI: 10.1016/0022-2828(88)90577-9. View

Rouslin W, Pullman M . Protonic inhibition of the mitochondrial adenosine 5'-triphosphatase in ischemic cardiac muscle. Reversible binding of the ATPase inhibitor protein to the mitochondrial ATPase during ischemia. J Mol Cell Cardiol. 1987; 19(7):661-8. DOI: 10.1016/s0022-2828(87)80374-7. View

Bronnikov G, Vinogradova S, Chernyak B . Regulation of ATP hydrolysis in liver mitochondria from ground squirrel. FEBS Lett. 1990; 266(1-2):83-6. DOI: 10.1016/0014-5793(90)81512-m. View

Panchenko M, Vinogradov A . Interaction between the mitochondrial ATP synthetase and ATPase inhibitor protein. Active/inactive slow pH-dependent transitions of the inhibitor protein. FEBS Lett. 1985; 184(2):226-30. DOI: 10.1016/0014-5793(85)80611-6. View

Schwerzmann K, Pedersen P . Proton--adenosinetriphosphatase complex of rat liver mitochondria: effect of energy state on its interaction with the adenosinetriphosphatase inhibitory peptide. Biochemistry. 1981; 20(22):6305-11. DOI: 10.1021/bi00525a004. View

Rouslin W, ERICKSON J, Solaro R . Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle. Am J Physiol. 1986; 250(3 Pt 2):H503-8. DOI: 10.1152/ajpheart.1986.250.3.H503. View

Chernyak B, Dukhovich V, Khodjaev EYu . The effect of the natural protein inhibitor on H+-ATPase hepatoma 22a mitochondria. FEBS Lett. 1987; 215(2):300-4. DOI: 10.1016/0014-5793(87)80166-7. View

Horstman L, RACKER E . Partial resolution of the enzyme catalyzing oxidative phosphorylation. XXII. Interaction between mitochondrial adenosine triphosphatase inhibitor and mitochondrial adenosine triphosphatase. J Biol Chem. 1970; 245(6):1336-44. View

10.

Rouslin W, Broge C . Regulation of mitochondrial matrix pH and adenosine 5'-triphosphatase activity during ischemia in slow heart-rate hearts. Role of Pi/H+ symport. J Biol Chem. 1989; 264(26):15224-9. View

11.

Rouslin W . Factors affecting the reactivation of the oligomycin-sensitive adenosine 5'-triphosphatase and the release of ATPase inhibitor protein during the re-energization of intact mitochondria from ischemic cardiac muscle. J Biol Chem. 1987; 262(8):3472-6. View

12.

Rouslin W . Protonic inhibition of the mitochondrial oligomycin-sensitive adenosine 5'-triphosphatase in ischemic and autolyzing cardiac muscle. Possible mechanism for the mitigation of ATP hydrolysis under nonenergizing conditions. J Biol Chem. 1983; 258(16):9657-61. View

13.

Chernyak B, Dukhovich V, Khodjaev EYu . Regulation of ATP hydrolysis in hepatoma 22a mitochondria. Arch Biochem Biophys. 1991; 286(2):604-9. DOI: 10.1016/0003-9861(91)90087-y. View

14.

Dreyfus G, Gomez-Puyou A . Electrochemical gradient induced displacement of the natural ATPase inhibitor protein from mitochondrial ATPase as directed by antibodies against the inhibitor protein. Biochem Biophys Res Commun. 1981; 100(1):400-6. DOI: 10.1016/s0006-291x(81)80110-6. View

15.

Rouslin W . Regulation of the mitochondrial ATPase in situ in cardiac muscle: role of the inhibitor subunit. J Bioenerg Biomembr. 1991; 23(6):873-88. DOI: 10.1007/BF00786006. View

16.

Khodjaev EYu , Komarnitsky F, Capozza G, Dukhovich V, Chernyak B, Papa S . Activation of a complex of ATPase with the natural protein inhibitor in submitochondrial particles. FEBS Lett. 1990; 272(1-2):145-8. DOI: 10.1016/0014-5793(90)80469-y. View

17.

Rouslin W . The mitochondrial adenosine 5'-triphosphatase in slow and fast heart rate hearts. Am J Physiol. 1987; 252(3 Pt 2):H622-7. DOI: 10.1152/ajpheart.1987.252.3.H622. View

18.

Rouslin W . Persistence of mitochondrial competence during myocardial autolysis. Am J Physiol. 1987; 252(5 Pt 2):H985-9. DOI: 10.1152/ajpheart.1987.252.5.H985. View

19.

Rouslin W, Broge C . Factors affecting the reactivation of the mitochondrial adenosine 5'-triphosphatase and the release of ATPase inhibitor protein during and following the reenergization of mitochondria from ischemic cardiac muscle. Arch Biochem Biophys. 1989; 275(2):385-94. DOI: 10.1016/0003-9861(89)90386-x. View

20.

Chernyak B, Khodjaev EYu , Kozlov I . The oxidation of sulfhydryl groups in mitochondrial F1-ATPase decreases the rate of its inactivation by the natural protein inhibitor. FEBS Lett. 1985; 187(2):253-6. DOI: 10.1016/0014-5793(85)81253-9. View