Note: Single-source report; awaiting corroboration.
Tau is a protein naturally present in the brain that supports neuron function and communication. In tauopathies, including Alzheimer’s disease and frontotemporal dementia, tau becomes excessively phosphorylated, forming toxic tangles harmful to brain cells. These neurodegenerative conditions often feature defects in cellular energy production linked to mitochondria.
Electrons typically travel through mitochondrial molecules to produce energy, but under certain conditions, this transfer can reverse—a process known as reverse electron transport that damages cells. Researchers at Stanford University, led by Dr. Bingwei Lu, investigated how abnormal tau influences this mitochondrial function in animal models, human brain tissue, and cultured cells. Their study was published in Neuron on August 6, 2026.
The team found that reverse electron transport was activated in models of tauopathy, and removing tau from cells prevented this activation. Hyperphosphorylated tau was seen entering mitochondria and interacting with electron transport chain components. This interaction altered mitochondrial protein relationships and triggered reverse electron transport. Stress alone did not activate this process in animals lacking tau. Additionally, increased reverse electron transport further elevated tau hyperphosphorylation, creating a harmful feedback loop.
These results suggest that hyperphosphorylated tau plays a key role in disrupting mitochondrial function through reverse electron transport, contributing to neurodegeneration. Interrupting this cycle by targeting tau or the reverse electron transport process could offer new therapeutic strategies for tau-related brain disorders.