Reduced Levels of Mitochondrial Complex I Subunit NDUFB8 and Linked Complex I + III Oxidoreductase Activity in the TgCRND8 Mouse Model of Alzheimer's Disease.

Journal of Alzheimer's disease : JAD

PubMedID: 24217272

Francis BM, Yang J, Song BJ, Gupta S, Maj M, Bazinet RP, Robinson B, Mount HT. Reduced Levels of Mitochondrial Complex I Subunit NDUFB8 and Linked Complex I + III Oxidoreductase Activity in the TgCRND8 Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2013;.
Bioenergetic failure is a feature of Alzheimer's disease (AD). We examined mitochondrial function in the amyloid-ß protein precursor transgenic 'TgCRND8' mouse model of AD. Activities of NADH: cytochrome c reductase (complex I + III) and cytochrome oxidase (complex IV) of the electron transport chain, as well as those of a-ketoglutarate dehydrogenase (a-KGDH) and pyruvate dehydrogenase (PDH) were assessed in brains of 45 week-old mice. Complex I + III activity was reduced by almost 50%, whereas complex IV, a-KGDH, and PDH activities were unaffected. Reduced activity coincided with decreased expression of NDUFB8, a nuclear-DNA encoded subunit integral to the assembly of complex I. The composition and availability of cardiolipin, a major phospholipid in inner mitochondrial membranes, was not altered. To determine whether mitochondrial output is affected by the selective reduction in complex I + III activity, we examined tissue levels of high-energy phosphates. ATP was maintained whereas creatine increased in the cortex and hippocampus. These results suggest disruption of complex I function and the likely role of creatine in sustaining ATP at late stages of dysfunction in TgCRND8 mice.