Mitochondrial Catalase and Oxidative InjuryBai J. · Cederbaum A.I.
Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, N.Y., USA
Mitochondria dysfunction induced by reactive oxygen species (ROS) is related to many human diseases and aging. In physiological conditions, the mitochondrial respiratory chain is the major source of ROS. ROS could be reduced by intracellular antioxidant enzymes including superoxide dismutase, glutathione peroxidase and catalase as well as some antioxidant molecules like glutathione and vitamin E. However, in pathological conditions, these antioxidants are often unable to deal with the large amount of ROS produced. This inefficiency of antioxidants is even more serious in mitochondria, because mitochondria in most cells lack catalase. Therefore, the excessive production of hydrogen peroxide in mitochondria will damage lipid, proteins and mDNA, which can then cause cells to die of necrosis or apoptosis. In order to study the important role of mitochondrial catalase in protecting cells from oxidative injury, a HepG2 cell line overexpressing catalase in mitochondria was developed by stable transfection of a plasmid containing catalase cDNA linked with a mitochondria leader sequence which would encode a signal peptide to lead catalase into the mitochondria. Mitochondria catalase was shown to protect cells from oxidative injury induced by hydrogen peroxide and antimycin A. However, it increased the sensitivity of cells to tumor necrosis factor-α-induced apoptosis by changing the redox-oxidative status in the mitochondria. Therefore, the antioxidative effectiveness of catalase when expressed in the mitochondrial compartment is dependent upon the oxidant and the locus of ROS production.
Dr. Arthur I. Cederbaum, Department of Biochemistry and
Molecular Biology, Box 1020, Mount Sinai School of Medicine
One Gustave L, Levy Place, New York, NY 10029 (USA)
Tel. +1 212 241 7285, Fax +1 212 996 7214
Number of Print Pages : 11
Number of Figures : 0, Number of Tables : 0, Number of References : 56
Biological Signals and Receptors
Vol. 10, No. 3-4, Year 2001 (Cover Date: May-August 2001)
Journal Editor: S.F. Pang, Hong Kong; P.A. Ward, Ann Arbor, Mich.; D.P. Cardinali, Buenos Aires
ISSN: 1422–4933 (print), 1422–4992 (Online)
For additional information: http://www.karger.com/journals/bsi