Table 3.

Tau and mitochondrial dynamics.

Model/disease	Tau isoform	Mitochondrial dynamics	References
HEK293 cells and rat primary hippocampal neurons	Human WT full length tau	Mitochondrial perinuclear accumulation. In HEK293 cells, hTau enhances expression of mitochondrial fusion proteins (Mfn1, Mfn2, and Opa1). In HEK293 cells, Mfn2 accumulation is due to hTau-mediated Mfn2 decreased polyubiquitination.	(195)
Primary cortical neurons (from tau KO mice)	Caspase-3 truncated tau (D421)	Mitochondrial fragmentation. Reduction of Opa1 levels.	(196)
RBE4 (rat brain ECs)	WT	Following treatment with okadaic acid (PP2A inhibitor), increased mitochondrial fission (Drp1 and Fis1) and fusion (Mfn1, Mfn2, and Opa1) protein levels.	(197)
Tg hTau mouse	Human WT full length tau	Hippocampal accumulation of Mfn1, Mfn2, and Opa1.	(195)
Tg4510 × Drp1+/−− mouse	P310L tau (neuronal expression)	Drp1 partial genetic ablation decreases Drp1 and Fis1 mRNA and protein levels, in cortical and hippocampal tissues. Drp1 partial genetic ablation increases Mfn1, Mfn2, and Opa1 mRNA and protein levels, in cortical and hippocampal tissues.	(198)
3xTg mouse and Alzheimer's disease	NFT	Excessive mitochondrial fission due to Drp1 and hyperphosphorylated tau interaction.	(199)
Alzheimer's disease	NFT	Disrupted balance of fission and fusion (mRNA and protein), shifted toward fission.	(200–202)