Minireview: on the Structure and Gating Mechanism of the Mitochondrial Channel, VDAC

Overview

Journal J Bioenerg Biomembr

Publisher Springer

Specialties Biochemistry
Biology
Endocrinology

Date 1998 Apr 29

PMID 9559853

Citations 32

Authors

C A Mannella

Affiliations

Soon will be listed here.

Abstract

There is considerable evidence that the voltage-gated mitochondrial channel VDAC forms a beta-barrel pore. Inferences about the number and tilt of beta-strands can be drawn from comparisons with bacterial beta-barrel pores whose structures have been determined by x-ray crystallography. A structural model for VDAC is proposed (based on sequence analysis and electron crystallography) in which the open state is like that of bacterial porins with several important differences. Because VDAC does not occur as close-packed trimers, there are probably fewer interpore contacts than in the bacterial porins. VDAC also appears to lack a large, fixed intraluminal segment and may not have as extensive a region of uniformly 35 degrees -tilted beta-strands as do the bacterial porins. These structural differences would be expected to render VDAC's beta-barrel less stable than its bacterial counterparts, making major conformational changes like those associated with gating more energetically feasible. A possible gating mechanism is suggested in which movement of the N-terminal alpha-helix out of the lumen wall triggers larger-scale structural changes.

Citing Articles

Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1.

Arif T, Shteinfer-Kuzmine A, Shoshan-Barmatz V Biomolecules. 2024; 14(10).

PMID: 39456237 PMC: 11506819. DOI: 10.3390/biom14101304.

Voltage-Dependent Anion Selective Channel 3: Unraveling Structural and Functional Features of the Least Known Porin Isoform.

Reina S, Checchetto V Front Physiol. 2022; 12:784867.

PMID: 35082690 PMC: 8784847. DOI: 10.3389/fphys.2021.784867.

VDAC1 is essential for neurite maintenance and the inhibition of its oligomerization protects spinal cord from demyelination and facilitates locomotor function recovery after spinal cord injury.

Paschon V, Morena B, Correia F, Beltrame G, Santos G, Cristante A Sci Rep. 2019; 9(1):14063.

PMID: 31575916 PMC: 6773716. DOI: 10.1038/s41598-019-50506-4.

Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics.

Shoshan-Barmatz V, Krelin Y, Shteinfer-Kuzmine A, Arif T Front Oncol. 2017; 7:154.

PMID: 28824871 PMC: 5534932. DOI: 10.3389/fonc.2017.00154.

Anion Channels of Mitochondria.

Ponnalagu D, Singh H Handb Exp Pharmacol. 2016; 240:71-101.

PMID: 27783269 PMC: 5855116. DOI: 10.1007/164_2016_39.

References

Forte M, Guy H, Mannella C . Molecular genetics of the VDAC ion channel: structural model and sequence analysis. J Bioenerg Biomembr. 1987; 19(4):341-50. DOI: 10.1007/BF00768537. View

Mannella C . Structural analysis of mitochondrial pores. Experientia. 1990; 46(2):137-45. DOI: 10.1007/BF02027309. View

Mannella C, Forte M, Colombini M . Toward the molecular structure of the mitochondrial channel, VDAC. J Bioenerg Biomembr. 1992; 24(1):7-19. DOI: 10.1007/BF00769525. View

Rostovtseva T, Colombini M . ATP flux is controlled by a voltage-gated channel from the mitochondrial outer membrane. J Biol Chem. 1996; 271(45):28006-8. DOI: 10.1074/jbc.271.45.28006. View

Mannella C . Phospholipase-induced crystallization of channels in mitochondrial outer membranes. Science. 1984; 224(4645):165-6. DOI: 10.1126/science.6322311. View

Shao L, Kinnally K, Mannella C . Circular dichroism studies of the mitochondrial channel, VDAC, from Neurospora crassa. Biophys J. 1996; 71(2):778-86. PMC: 1233534. DOI: 10.1016/S0006-3495(96)79277-9. View

Thomas L, Blachly-Dyson E, Colombini M, Forte M . Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel. Proc Natl Acad Sci U S A. 1993; 90(12):5446-9. PMC: 46737. DOI: 10.1073/pnas.90.12.5446. View

Neuwald A, Liu J, Lawrence C . Gibbs motif sampling: detection of bacterial outer membrane protein repeats. Protein Sci. 1995; 4(8):1618-32. PMC: 2143180. DOI: 10.1002/pro.5560040820. View

Blachly-Dyson E, Peng S, Colombini M, Forte M . Selectivity changes in site-directed mutants of the VDAC ion channel: structural implications. Science. 1990; 247(4947):1233-6. DOI: 10.1126/science.1690454. View

10.

Weiss M, Kreusch A, Schiltz E, Nestel U, Welte W, Weckesser J . The structure of porin from Rhodobacter capsulatus at 1.8 A resolution. FEBS Lett. 1991; 280(2):379-82. DOI: 10.1016/0014-5793(91)80336-2. View

11.

Zizi M, Thomas L, Blachly-Dyson E, Forte M, Colombini M . Oriented channel insertion reveals the motion of a transmembrane beta strand during voltage gating of VDAC. J Membr Biol. 1995; 144(2):121-9. DOI: 10.1007/BF00232798. View

12.

Benz R, Kottke M, Brdiczka D . The cationically selective state of the mitochondrial outer membrane pore: a study with intact mitochondria and reconstituted mitochondrial porin. Biochim Biophys Acta. 1990; 1022(3):311-8. DOI: 10.1016/0005-2736(90)90279-w. View

13.

Zizi M, Forte M, Blachly-Dyson E, Colombini M . NADH regulates the gating of VDAC, the mitochondrial outer membrane channel. J Biol Chem. 1994; 269(3):1614-6. View

14.

Lawrence C, Altschul S, Boguski M, Liu J, Neuwald A, Wootton J . Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. Science. 1993; 262(5131):208-14. DOI: 10.1126/science.8211139. View

15.

De Pinto V, Prezioso G, Thinnes F, Link T, Palmieri F . Peptide-specific antibodies and proteases as probes of the transmembrane topology of the bovine heart mitochondrial porin. Biochemistry. 1991; 30(42):10191-200. DOI: 10.1021/bi00106a017. View

16.

Guo X, Mannella C . Conformational change in the mitochondrial channel, VDAC, detected by electron cryo-microscopy. Biophys J. 1993; 64(2):545-9. PMC: 1262358. DOI: 10.1016/S0006-3495(93)81399-7. View

17.

Song J, Colombini M . Indications of a common folding pattern for VDAC channels from all sources. J Bioenerg Biomembr. 1996; 28(2):153-61. DOI: 10.1007/BF02110646. View

18.

Song L, Hobaugh M, Shustak C, Cheley S, Bayley H, Gouaux J . Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science. 1996; 274(5294):1859-66. DOI: 10.1126/science.274.5294.1859. View

19.

Weiss M, Schulz G . Structure of porin refined at 1.8 A resolution. J Mol Biol. 1992; 227(2):493-509. DOI: 10.1016/0022-2836(92)90903-w. View

20.

Cowan S, Schirmer T, Rummel G, Steiert M, Ghosh R, Pauptit R . Crystal structures explain functional properties of two E. coli porins. Nature. 1992; 358(6389):727-33. DOI: 10.1038/358727a0. View