| First Author | Yang L | Year | 2009 |
| Journal | Neurobiol Dis | Volume | 36 |
| Issue | 2 | Pages | 320-30 |
| PubMed ID | 19660549 | Mgi Jnum | J:222374 |
| Mgi Id | MGI:5644415 | Doi | 10.1016/j.nbd.2009.07.023 |
| Citation | Yang L, et al. (2009) Mice deficient in dihydrolipoyl succinyl transferase show increased vulnerability to mitochondrial toxins. Neurobiol Dis 36(2):320-30 |
| abstractText | The activity of a key mitochondrial tricarboxylic acid cycle enzyme, alpha-ketoglutarate dehydrogenase complex (KGDHC), declines in many neurodegenerative diseases. KGDHC consists of three subunits. The dihydrolipoyl succinyl transferase (DLST) component is unique to KGDHC. DLST(+/-) mice showed reduced mRNA and protein levels and decreased brain mitochondrial KGDHC activity. Neurotoxic effects of mitochondrial toxins were exacerbated in DLST(+/-) mice. MPTP produced a significantly greater reduction of striatal dopamine and tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta of DLST(+/-) mice. DLST deficiency enhanced the severity of lipid peroxidation in the substantia nigra after MPTP treatment. Striatal lesions induced by either malonate or 3-nitropropionic acid (3-NP) were significantly larger in DLST(+/-) mice than in wildtype controls. DLST deficiency enhanced the 3-NP inhibition of mitochondria enzymes, and 3-NP induced protein and DNA oxidations. These observations support the hypothesis that reductions in KGDHC may impair the adaptability of the brain and contribute to the pathogenesis of neurodegenerative diseases. |
