Human wild-type full-length tau accumulation disrupts mitochondrial dynamics and the functions via increasing mitofusins

• DOI: 10.1038/srep24756
• Publication Date: 2016-04-21T09:22:54Z
• Authors: Xia-Chun Li; Yu Hu; Zhi-hao Wang; Yu Luo; Yao Zhang; Xiu-Ping Liu; Qiong Feng; Qun Wang; Keqiang Ye; Gong-Ping Liu; Jian-Zhi Wang
• Keywords: MFN2; MFN1

Abstract Intracellular accumulation of tau protein is hallmark sporadic Alzheimer’s disease (AD), however, the cellular mechanism whereby causes neurodegeneration poorly understood. Here we report that overexpression human wild-type full-length (termed htau) disrupted mitochondrial dynamics by enhancing fusion and induced their perinuclear in HEK293 cells rat primary hippocampal neurons. The htau at later stage inhibited functions shown decreased ATP level, ratio ATP/ADP complex I activity. Simultaneously, cell viability was with retraction cellular/neuronal processes. Further studies demonstrated increased proteins, including OPA1 mitofusins (Mfn1, Mfn2) reduced ubiquitination Mfn2. Downregulation shRNA to ~45% or ~52% control levels attenuated htau-enhanced restored functions, while downregulation ~50% level did not show rescue effects. Finally, abnormal dysfunction were also observed brains transgenic mice. Taken together, our data demonstrate decreases degeneration via mitofusin-associated fusion, which provides new insights into molecular mechanisms underlying tauopathies.