Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Jun;53(6):885-92.
doi: 10.1161/HYPERTENSIONAHA.109.130054. Epub 2009 Apr 27.

Mitochondria and reactive oxygen species

Francesco Addabbo  1 , Monica Montagnani, Michael S Goligorsky
Affiliations
Review

Mitochondria and reactive oxygen species

Francesco Addabbo et al. Hypertension. 2009 Jun.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic illustration of the Warburg effect in tumor cells and in early asymptomatic endothelial cell dysfunction. Under normoxic conditions, intact cells metabolize glucose through the TCA cycle. In contrast, tumor cells avidly uptake glucose and exhibit blockade of oxidative phosphorylation at the entry point of conversion of lactate to pyruvate because of the inhibition of pyruvate dehydrogenase kinase-1 (PDK-1). In addition, mutations of p53 result in the reduced signaling through TP53-induced glycolysis and apoptosis regulator (TIGAR), which normally inhibits the glycolytic pathway. As a result, lactate is produced in excessive amounts, all hallmarks of the Warburg effect. Interestingly, pharmacological inhibitors of lactate dehydrogenase (LDH) may reverse glucose metabolism to oxidative phosphorylation. At the early stages of endothelial cell dysfunction, similar to tumor cells, oxidative phosphorylation is suppressed and glycolysis enhanced, resulting in overproduction of lactate. Under these conditions, blockade of the TCA cycle occurs at the level of the catalyzed by ECHS-1 conversion of acyl-CoA to acetyl-CoA, the point of entry to the cycle, and at the level of the conversion of citrate to isocitrate (because of the depletion of aconitase 2). This block in the TCA cycle can be resolved by bypassing the deficient aconitase 2 with the downstream substrate, α-ketoglutarate (Alpha-KG). These new data on the early metabolic stigmata of dysfunctional endothelia vis-à-vis tumor cells emphasize their similarities and distinctions.
See this image and copyright information in PMC

References

    1. Thomas L. The Lives of a Cell: Notes of a Biology Watcher. Toronto, Canada: Bantam Books, Inc; 1975.
    1. Skulachev VP. Chemiosmotic concept of the membrane bioenergetics: what is already clear and what is still waiting for elucidation? J Bioenerg Biomembr. 1994;26:589–598. - PubMed
    1. Wallace KB, Starkov AA. Mitochondrial targets of drug toxicity. Annu Rev Pharmacol Toxicol. 2000;40:353–388. - PubMed
    1. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787–795. - PubMed
    1. St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem. 2002;277:44784–44790. - PubMed

Publication types

MeSH terms

Substances