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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lemeshko, Victor V. |
| Description | Author Affiliation: Lemeshko VV ( Escuela de Física, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Medellín, Calle 59A, No 63-20, Medellín, Colombia. Electronic address: vvasilie@unal.edu.co.) |
| Abstract | Mitochondrial hexokinase (HK) and creatine kinase (CK) known to form complexes with a voltage dependent anion channel (VDAC) have been reported to increase cell death resistance under hypoxia/anoxia. In this work we propose a new, non-Mitchell mechanism of generation of the inner and outer membrane potentials at anaerobic conditions. The driving force is provided by the Gibbs free energy of the HK and CK reactions associated with the VDAC–HK and the ANT (adenine nucleotide translocator)–CK–VDAC complexes, respectively, both functioning as voltage generators. In the absence of oxygen, the cytosolic creatine phosphate can be directly used by the ANT–CK–VDAC contact sites to produce ATP from ADP in the mitochondrial matrix. After that, ATP released through the fraction of unbound ANTs in exchange for ADP is used in the mitochondrial intermembrane space by the outer membrane VDAC–HK electrogenic complexes to convert cytosolic glucose into glucose-6-phosphate. A simple computational model based on the application of Ohm's law to an equivalent electrical circuit showed a possibility of generation of the inner membrane potential up to − 160 mV, under certain conditions, and of relatively high outer membrane potential without wasting of ATP that normally leads to cell death. The calculated membrane potentials depended on the restriction of ATP/ADP diffusion in narrow cristae and through the cristae junctions. We suggest that high inner membrane potential and calcium extrusion from the mitochondrial intermembrane space by generated positive outer membrane potential prevent mitochondrial permeability transition, thus allowing the maintenance of mitochondrial integrity and cell survival in the absence of oxygen. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 7 |
| Volume Number | 1838 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-07-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Membrane Potential, Mitochondrial Physiology Mitochondria Mitochondrial Membranes Adenosine Diphosphate Metabolism Adenosine Triphosphate Calcium Cell Death Creatine Kinase Cytosol Glucose Glucose-6-Phosphate Hexokinase Oxygen Phosphocreatine Voltage-Dependent Anion Channels Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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