PMID- 22305999
OWN - NLM
STAT- MEDLINE
DCOM- 20120521
LR  - 20220317
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Print)
IS  - 1063-4584 (Linking)
VI  - 20
IP  - 4
DP  - 2012 Apr
TI  - Mitochondrial electron transport and glycolysis are coupled in articular 
      cartilage.
PG  - 323-9
LID - 10.1016/j.joca.2012.01.003 [doi]
AB  - OBJECTIVE: Although the majority of the adenosine triphosphate (ATP) in 
      chondrocytes is made by glycolysis rather than by oxidative phosphorylation in 
      mitochondria there is evidence to suggest that reactive oxygen species produced 
      by mitochondrial electron transport (ET) help to maintain cellular redox balance 
      in favor of glycolysis. The objective of this study was to test this hypothesis 
      by determining if rotenone, which inhibits ET and blocks oxidant production 
      inhibits glycolytic ATP synthesis. DESIGN: Bovine osteochondral explants were 
      treated with rotenone, an ET inhibitor; or oligomycin an ATP synthase inhibitor; 
      or 2-fluoro-2-deoxy-D-glucose, a glycolysis inhibiter; or peroxide, an exogenous 
      oxidant; or mitoquinone (MitoQ), a mitochondria-targeted anti-oxidant. Cartilage 
      extracts were assayed for ATP, nicotine adenine dinucleotide (NAD+/H), and 
      culture medium was assayed for pyruvate and lactate after 24 h of treatment. 
      Imaging studies were used to measure superoxide production in cartilage. RESULTS: 
      Rotenone and 2-FG caused a significant decline in cartilage ATP (P < 0.001). In 
      contrast, ATP levels were not affected by oligomycin. Peroxide treatment blocked 
      rotenone effects on ATP, while treatment with MitoQ significantly suppressed ATP 
      levels. Rotenone and 2-FG caused a significant decline in pyruvate, but not in 
      lactate production. NADH:NAD+ ratios decreased significantly in both rotenone and 
      2-FG-treated explants (P < 0.05). Rotenone also significantly reduced superoxide 
      production. CONCLUSIONS: These findings showing a link between glycolysis and ET 
      are consistent with previous reports on the critical need for oxidants to support 
      normal chondrocyte metabolism. They suggest a novel role for mitochondria in 
      cartilage homeostasis that is independent of oxidative phosphorylation.
CI  - Copyright A(c) 2012 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Martin, J A
AU  - Martin JA
AD  - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and 
      Clinics, Iowa City, IA, USA. james-martin@uiowa.edu
FAU - Martini, A
AU  - Martini A
FAU - Molinari, A
AU  - Molinari A
FAU - Morgan, W
AU  - Morgan W
FAU - Ramalingam, W
AU  - Ramalingam W
FAU - Buckwalter, J A
AU  - Buckwalter JA
FAU - McKinley, T O
AU  - McKinley TO
LA  - eng
GR  - P50 AR055533/AR/NIAMS NIH HHS/United States
GR  - P50 AR055533-01/AR/NIAMS NIH HHS/United States
GR  - 1 P50 AR055533/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120116
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Uncoupling Agents)
RN  - 03L9OT429T (Rotenone)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 11062-77-4 (Superoxides)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/biosynthesis
MH  - Animals
MH  - Cartilage, Articular/*metabolism
MH  - Cattle
MH  - Chondrocytes/metabolism
MH  - Electron Transport/drug effects/physiology
MH  - Fluorodeoxyglucose F18/pharmacology
MH  - Glycolysis/drug effects/physiology
MH  - Mitochondria/drug effects/*metabolism
MH  - Rotenone/pharmacology
MH  - Superoxides/metabolism
MH  - Tissue Culture Techniques
MH  - Uncoupling Agents/pharmacology
PMC - PMC3634328
MID - NIHMS356014
EDAT- 2012/02/07 06:00
MHDA- 2012/05/23 06:00
PMCR- 2013/04/24
CRDT- 2012/02/07 06:00
PHST- 2010/12/29 00:00 [received]
PHST- 2011/12/06 00:00 [revised]
PHST- 2012/01/10 00:00 [accepted]
PHST- 2012/02/07 06:00 [entrez]
PHST- 2012/02/07 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
PHST- 2013/04/24 00:00 [pmc-release]
AID - S1063-4584(12)00024-6 [pii]
AID - 10.1016/j.joca.2012.01.003 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2012 Apr;20(4):323-9. doi: 10.1016/j.joca.2012.01.003. 
      Epub 2012 Jan 16.