PMID- 24081983
OWN - NLM
STAT- MEDLINE
DCOM- 20140722
LR  - 20211021
IS  - 1540-7748 (Electronic)
IS  - 0022-1295 (Print)
IS  - 0022-1295 (Linking)
VI  - 142
IP  - 4
DP  - 2013 Oct
TI  - Hexokinase-mitochondrial interactions regulate glucose metabolism differentially 
      in adult and neonatal cardiac myocytes.
PG  - 425-36
LID - 10.1085/jgp.201310968 [doi]
AB  - In mammalian tumor cell lines, localization of hexokinase (HK) isoforms to the 
      cytoplasm or mitochondria has been shown to control their anabolic (glycogen 
      synthesis) and catabolic (glycolysis) activities. In this study, we examined 
      whether HK isoform differences could explain the markedly different metabolic 
      profiles between normal adult and neonatal cardiac tissue. We used a set of novel 
      genetically encoded optical imaging tools to track, in real-time in isolated 
      adult (ARVM) and neonatal (NRVM) rat ventricular myocytes, the subcellular 
      distributions of HKI and HKII, and the functional consequences on glucose 
      utilization. We show that HKII, the predominant isoform in ARVM, dynamically 
      translocates from mitochondria and cytoplasm in response to removal of 
      extracellular glucose or addition of iodoacetate (IAA). In contrast, HKI, the 
      predominant isoform in NRVM, is only bound to mitochondria and is not displaced 
      by the above interventions. In ARVM, overexpression of HKI, but not HKII, 
      increased glycolytic activity. In neonatal rat ventricular myocytes (NVRM), 
      knockdown of HKI, but not HKII, decreased glycolytic activity. In conclusion, 
      differential interactions of HKI and HKII with mitochondria underlie the 
      different metabolic profiles of ARVM and NRVM, accounting for the markedly 
      increased glycolytic activity of NRVM.
FAU - Calmettes, Guillaume
AU  - Calmettes G
AD  - UCLA Cardiovascular Research Laboratory, 2 Department of Medicine (Cardiology), 
      and 3 Department of Physiology, David Geffen School of Medicine at UCLA, Los 
      Angeles, CA 90095.
FAU - John, Scott A
AU  - John SA
FAU - Weiss, James N
AU  - Weiss JN
FAU - Ribalet, Bernard
AU  - Ribalet B
LA  - eng
GR  - P50 HL080111/HL/NHLBI NIH HHS/United States
GR  - P01 HL080111/HL/NHLBI NIH HHS/United States
GR  - HHSN268201000035C/HL/NHLBI NIH HHS/United States
GR  - R01 HL095663/HL/NHLBI NIH HHS/United States
GR  - R01 HL071870/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Gen Physiol
JT  - The Journal of general physiology
JID - 2985110R
RN  - 0 (Isoenzymes)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cytoplasm/metabolism
MH  - Glucose/*metabolism
MH  - Glycolysis
MH  - Heart Ventricles/cytology/*growth & development/metabolism
MH  - Hexokinase/*metabolism
MH  - Isoenzymes/metabolism
MH  - Mitochondria/*metabolism
MH  - Myocytes, Cardiac/enzymology/*metabolism
MH  - Protein Transport
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC3787771
EDAT- 2013/10/02 06:00
MHDA- 2014/07/23 06:00
PMCR- 2014/04/01
CRDT- 2013/10/02 06:00
PHST- 2013/10/02 06:00 [entrez]
PHST- 2013/10/02 06:00 [pubmed]
PHST- 2014/07/23 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - jgp.201310968 [pii]
AID - 201310968 [pii]
AID - 10.1085/jgp.201310968 [doi]
PST - ppublish
SO  - J Gen Physiol. 2013 Oct;142(4):425-36. doi: 10.1085/jgp.201310968.