PMID- 26732303
OWN - NLM
STAT- MEDLINE
DCOM- 20160712
LR  - 20201209
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 581
IP  - 1
DP  - 2016 Apr 25
TI  - Mg(++) requirement for MtHK binding, and Mg(++) stabilization of mitochondrial 
      membranes via activation of MtHK & MtCK and promotion of mitochondrial 
      permeability transition pore closure: A hypothesis on mechanisms underlying 
      Mg(++)'s antioxidant and cytoprotective effects.
PG  - 1-13
LID - S0378-1119(15)01544-9 [pii]
LID - 10.1016/j.gene.2015.12.046 [doi]
AB  - Evidence points to magnesium's antioxidant, anti-necrotic, and anti-apoptotic 
      effects in cardio- and neuroprotection. With magnesium being involved in over 300 
      biochemical reactions, the mechanisms underlying its cytoprotective and 
      antioxidant effects have remained elusive. The profound anti-apoptotic, anabolic, 
      and antioxidant effects of mitochondrion bound hexokinase (MtHk), and the 
      anti-apoptotic, anti-necrotic, and antioxidant functions of mitochondrial 
      creatine kinase (MtCK) have been established over the past few decades. As 
      powerful regulators of the mitochondrial permeability transition pore (PTP), MtHK 
      and MtCK promote anti-apoptosis and anti-necrosis by stabilizing mitochondrial 
      outer and inner membranes. In this article, it is proposed that magnesium is 
      essentially and directly involved in mitochondrial membrane stabilization via (i) 
      Mg(++) ion requirement for the binding of mitochondrial hexokinase (ii) Mg(++)'s 
      allosteric activation of mitochondrial bound hexokinase, and stimulation of 
      mitochondrial bound creatine kinase activities, and (iii) Mg(++) inhibition of 
      PTP opening by Ca(++) ions. These effects of Mg(++) ions are indirectly 
      supplanted by the stimulatory effect of magnesium on the Akt kinase survival 
      pathway. The "Magnesium/Calcium Yin Yang Hypothesis" proposes here that because 
      of the antagonistic effects of Ca(++) and Mg(++) ions in the presence of high 
      Ca(++) ion concentration at MtHK, MtCK, and PTP, magnesium supplementation may 
      provide cytoprotective effects in the treatment of some degenerative diseases and 
      cytopathies with high intracellular [Ca(++)]/ [Mg(++)] ratio at these sites, 
      whether of genetic, developmental, drug induced, ischemic, immune based, toxic, 
      or infectious etiology.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Golshani-Hebroni, Shiva
AU  - Golshani-Hebroni S
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20151228
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Antioxidants)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - I38ZP9992A (Magnesium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Calcium/metabolism
MH  - *Cold Temperature
MH  - Creatine Kinase/metabolism
MH  - Enzyme Activation
MH  - Hexokinase/*metabolism
MH  - Magnesium/*metabolism
MH  - Mitochondrial Membrane Transport Proteins/*metabolism
MH  - Mitochondrial Membranes/*enzymology
MH  - Mitochondrial Permeability Transition Pore
MH  - Protein Binding
OTO - NOTNLM
OT  - ATP synthase
OT  - Magnesium
OT  - anti-apoptosis
OT  - anti-necrosis
OT  - antioxidant
OT  - apoptosis
OT  - calcium
OT  - cardioprotection
OT  - cytoprotection
OT  - degenerative disease
OT  - hexokinase
OT  - mitochondrial bound hexokinase
OT  - mitochondrial creatine kinase
OT  - mitochondrial permeability transition pore
OT  - necrosis
OT  - neuroprotection
EDAT- 2016/01/07 06:00
MHDA- 2016/07/13 06:00
CRDT- 2016/01/07 06:00
PHST- 2015/05/09 00:00 [received]
PHST- 2015/12/15 00:00 [revised]
PHST- 2015/12/16 00:00 [accepted]
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2016/07/13 06:00 [medline]
AID - S0378-1119(15)01544-9 [pii]
AID - 10.1016/j.gene.2015.12.046 [doi]
PST - ppublish
SO  - Gene. 2016 Apr 25;581(1):1-13. doi: 10.1016/j.gene.2015.12.046. Epub 2015 Dec 28.