Hydroxynonenal and uncoupling proteins: a model for protection against oxidative damage.
In this mini review we summarize recent studies from our laboratory that show the involvement of superoxide and the lipid peroxidation product 4-hydroxynonenal in the regulation of mitochondrial uncoupling. Superoxide produced during mitochondrial respiration is a major cause of the cellular oxidative damage that may underlie degenerative diseases and ageing. Superoxide production is very sensitive to the magnitude of the mitochondrial protonmotive force, so can be strongly decreased by mild uncoupling. Superoxide is able to give rise to other reactive oxygen species, which elicit deleterious effects primarily by oxidizing intracellular components, including lipids, DNA and proteins. Superoxide-induced lipid peroxidation leads to the production of reactive aldehydes, including 4-hydroxynonenal. These aldehydic lipid peroxidation products are in turn able to modify proteins such as mitochondrial uncoupling proteins and the adenine nucleotide translocase, converting them into active proton transporters. This activation induces mild uncoupling and so diminishes mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of energy production.
Echtay
Karim S
KS
Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon. karim.echtay@balamand.edu.lb
Pakay
Julian L
JL
Esteves
Telma C
TC
Brand
Martin D
MD
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects; D006801:Humans; D007473:Ion Channels; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress; D010101:Oxygen Consumption; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology*; D000071256:Uncoupling Protein 1
D000447:Aldehydes; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D013481:Superoxides; D000226:Mitochondrial ADP, ATP Translocases; C027576:4-hydroxy-2-nonenal