Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease

作者：Zhang Liang; Trushin Sergey; Christensen Trace A; Bachmeier Benjamin V; Gateno Benjamin; Schroeder Andreas; Yao Jia; Itoh Kie; Sesaki Hiromi; Poon Wayne W; Gylys Karen H; Patterson Emily R; Parisi Joseph E; Brinton Roberta Diaz; Sali**ury Jeffrey L; Trushina Eugenia^*

来源：Scientific Reports, 2016, 6(1): 18725.

DOI：10.1038/srep18725

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.

• 出版日期2016-1-5