Journal article
Mitochondrial Electron Transport and Glycolysis are coupled in Articular Cartilage
Osteoarthritis and cartilage, Vol.20(4), pp.323-329
04/2012
DOI: 10.1016/j.joca.2012.01.003
PMCID: PMC3634328
PMID: 22305999
Abstract
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.
Details
- Title: Subtitle
- Mitochondrial Electron Transport and Glycolysis are coupled in Articular Cartilage
- Creators
- James A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAAnne Martini - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAAlexander Molinari - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAWalter Morgan - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAWendy Ramalingam - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAJoseph A Buckwalter - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USATodd O McKinley - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Osteoarthritis and cartilage, Vol.20(4), pp.323-329
- DOI
- 10.1016/j.joca.2012.01.003
- PMID
- 22305999
- PMCID
- PMC3634328
- NLM abbreviation
- Osteoarthritis Cartilage
- ISSN
- 1063-4584
- eISSN
- 1522-9653
- Grant note
- P50 AR055533-01 || AR / National Institute of Arthritis and Musculoskeletal and Skin Diseases : NIAMS
- Language
- English
- Date published
- 04/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
- Record Identifier
- 9984040394202771
Metrics
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