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Mitochondrial Aconitase is a Transglutaminase 2 Substrate: Transglutamination is a Probable Mechanism Contributing to High-Molecular-Weight Aggregates of Aconitase and Loss of Aconitase Activity in Huntington Disease Brain |
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| Authors: | Soo-Youl Kim Lyuben Marekov Parvesh Bubber Susan E Browne Irina Stavrovskaya Jongmin Lee Peter M Steinert John P Blass M Flint Beal Gary E Gibson Arthur J L Cooper |
| Institution: | (1) Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA;(2) Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA;(3) Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA;(4) Burke Medical Research Institute, White Plains, NY 10605, USA;(5) Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA;(6) Division of Basic Sciences, National Cancer Center, 809 Madu-dong Ilsandong-gu, Goyang, Kyonggi-do, 410-351, Republic of Korea |
| Abstract: | Transglutaminase activity was found to be present in highly purified non-synaptosomal rat brain mitochondria. A 78-kDa protein in these organelles was shown to be a transglutaminase 2 substrate, and incubation of a non-synaptosomal mitochondrial lysate with transglutaminase 2 yielded high-Mr proteins. The 78-kDa protein was identified as mitochondrial aconitase by MALDI-TOF analysis. Aconitase activity was decreased in a dose-dependent manner when non-synaptosomal rat brain mitochondria were incubated with transglutaminase 2. Transglutaminase activity is increased about 2-fold in the mitochondrial fraction of HD caudate. Moreover, Western blotting of the mitochondrial fraction revealed that most of the mitochondrial aconitase in HD caudate is present as high-Mr aggregates. Aconitase activity was previously shown to be decreased in Huntington disease (HD) caudate (a region severely damaged by the disease). The present findings suggest that an increase of transglutaminase activity in HD caudate may contribute to mitochondrial dysfunction by incorporating aconitase into inactive polymers. |
| Keywords: | Huntington disease mitochondrial aconitase non-synaptosomal mitochondria transglutaminase |
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