PMID- 24565793
OWN - NLM
STAT- MEDLINE
DCOM- 20140724
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1838
IP  - 7
DP  - 2014 Jul
TI  - VDAC electronics: 2. A new, anaerobic mechanism of generation of the membrane 
      potentials in mitochondria.
PG  - 1801-8
LID - S0005-2736(14)00071-6 [pii]
LID - 10.1016/j.bbamem.2014.02.007 [doi]
AB  - 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 -160mV, 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.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Lemeshko, Victor V
AU  - Lemeshko VV
AD  - Escuela de Fisica, Facultad de Ciencias, Universidad Nacional de Colombia, Sede 
      Medellin, Calle 59A, No 63-20, Medellin, Colombia. Electronic address: 
      vvasilie@unal.edu.co.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140222
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Voltage-Dependent Anion Channels)
RN  - 020IUV4N33 (Phosphocreatine)
RN  - 56-73-5 (Glucose-6-Phosphate)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Diphosphate/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Calcium/metabolism
MH  - Cell Death/physiology
MH  - Creatine Kinase/metabolism
MH  - Cytosol/metabolism/physiology
MH  - Glucose/metabolism
MH  - Glucose-6-Phosphate/metabolism
MH  - Hexokinase/metabolism
MH  - Membrane Potential, Mitochondrial/*physiology
MH  - Mitochondria/metabolism/*physiology
MH  - Mitochondrial Membranes/metabolism/*physiology
MH  - Oxygen/metabolism
MH  - Phosphocreatine/metabolism
MH  - Voltage-Dependent Anion Channels/metabolism
OTO - NOTNLM
OT  - Aerobic glycolysis
OT  - Creatine kinase
OT  - Hexokinase
OT  - VDAC
EDAT- 2014/02/26 06:00
MHDA- 2014/07/25 06:00
CRDT- 2014/02/26 06:00
PHST- 2013/11/08 00:00 [received]
PHST- 2014/01/08 00:00 [revised]
PHST- 2014/02/12 00:00 [accepted]
PHST- 2014/02/26 06:00 [entrez]
PHST- 2014/02/26 06:00 [pubmed]
PHST- 2014/07/25 06:00 [medline]
AID - S0005-2736(14)00071-6 [pii]
AID - 10.1016/j.bbamem.2014.02.007 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2014 Jul;1838(7):1801-8. doi: 10.1016/j.bbamem.2014.02.007. 
      Epub 2014 Feb 22.