PMID- 23993956
OWN - NLM
STAT- MEDLINE
DCOM- 20140715
LR  - 20211203
IS  - 1872-8278 (Electronic)
IS  - 1567-7249 (Print)
IS  - 1567-7249 (Linking)
VI  - 13
IP  - 6
DP  - 2013 Nov
TI  - Light activation of the insulin receptor regulates mitochondrial hexokinase. A 
      possible mechanism of retinal neuroprotection.
PG  - 566-76
LID - S1567-7249(13)00238-9 [pii]
LID - 10.1016/j.mito.2013.08.005 [doi]
AB  - The serine/threonine kinase Akt has been shown to mediate the anti-apoptotic 
      activity through hexokinase (HK)-mitochondria interaction. We previously reported 
      that Akt activation in retinal rod photoreceptor cells is mediated through the 
      light-dependent insulin receptor (IR)/PI3K pathway. Our data indicate that 
      light-induced activation of IR/PI3K/Akt results in the translocation of HK-II to 
      mitochondria. We also found that PHLPPL, a serine/threonine phosphatase, enhanced 
      the binding of HK-II to mitochondria. We found a mitochondrial targeting signal 
      in PHLPPL and our study suggests that Akt translocation to mitochondria could be 
      mediated through PHLPPL. Our results suggest that the light-dependent IR/PI3K/Akt 
      pathway regulates hexokinase-mitochondria interaction in photoreceptors. 
      Down-regulation of IR signaling has been associated with ocular diseases of 
      retinitis pigmentosa, diabetic retinopathy, and Leber Congenital Amaurosis-type 
      2, and agents that enhance the binding interaction between hexokinase and 
      mitochondria may have therapeutic potential against these ocular diseases.
CI  - (c) 2013.
FAU - Rajala, Ammaji
AU  - Rajala A
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA; Dean A. McGee Eye Institute, Oklahoma City, OK 73104, 
      USA.
FAU - Gupta, Vivek K
AU  - Gupta VK
FAU - Anderson, Robert E
AU  - Anderson RE
FAU - Rajala, Raju V S
AU  - Rajala RV
LA  - eng
GR  - P20 RR017703/RR/NCRR NIH HHS/United States
GR  - RR17703/RR/NCRR NIH HHS/United States
GR  - R01 EY000871/EY/NEI NIH HHS/United States
GR  - P30 EY021725/EY/NEI NIH HHS/United States
GR  - EY021725/EY/NEI NIH HHS/United States
GR  - EY016507/EY/NEI NIH HHS/United States
GR  - EY00871/EY/NEI NIH HHS/United States
GR  - R01 EY016507/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130830
PL  - Netherlands
TA  - Mitochondrion
JT  - Mitochondrion
JID - 100968751
RN  - 0 (DNA Primers)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PHB protein, human)
RN  - 0 (Prohibitins)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.3.16 (PHLPP1 protein, rat)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - HEK293 Cells
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - *Light
MH  - Mitochondria/*enzymology
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/chemistry/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Prohibitins
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Insulin/metabolism/*radiation effects
MH  - Retina/enzymology/metabolism/*radiation effects
MH  - Signal Transduction
PMC - PMC3818532
MID - NIHMS522127
OTO - NOTNLM
OT  - GSK-3beta
OT  - Glycogen synthase kinase
OT  - HK-II
OT  - HSP60
OT  - Hexokinase
OT  - IR
OT  - Insulin receptor
OT  - Mitochondria
OT  - Neuroprotection
OT  - PH domain and leucine-rich repeat protein phosphatase-like
OT  - PHB1
OT  - PHLPPL
OT  - PI3K
OT  - Phosphoinositide 3-kinase
OT  - ROS
OT  - VDAC
OT  - glycogen synthase kinase-3beta
OT  - heat shock protein 60
OT  - hexokinase
OT  - insulin receptor
OT  - phosphoinositide 3-kinase
OT  - prohibitin-1
OT  - rod outer segments
OT  - voltage-dependent anion channel
EDAT- 2013/09/03 06:00
MHDA- 2014/07/16 06:00
PMCR- 2014/11/01
CRDT- 2013/09/03 06:00
PHST- 2013/04/29 00:00 [received]
PHST- 2013/08/03 00:00 [revised]
PHST- 2013/08/15 00:00 [accepted]
PHST- 2013/09/03 06:00 [entrez]
PHST- 2013/09/03 06:00 [pubmed]
PHST- 2014/07/16 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - S1567-7249(13)00238-9 [pii]
AID - 10.1016/j.mito.2013.08.005 [doi]
PST - ppublish
SO  - Mitochondrion. 2013 Nov;13(6):566-76. doi: 10.1016/j.mito.2013.08.005. Epub 2013 
      Aug 30.