Tau-induced mitochondrial reverse electron transport drives neurodegeneration.

Tau regulates mitochondrial reverse electron transport, producing excess reactive oxygen species and driving neurodegeneration in tauopathies.

• Why it matters: Understanding how tau abnormalities lead to mitochondrial dysfunction is crucial for developing targeted therapies for neurodegenerative diseases like Alzheimer’s.
• What they did: The study used flies, mice, and human neurons to show that tau interacts with mitochondrial complex I subunit NDUFS3, promoting RET in a phosphorylation-dependent way, especially under stress or aging.
• The result: Inhibiting RET reduces tau toxicity across species, revealing tau’s normal role in mitochondria and offering a new therapeutic target for conditions involving tau pathology and mitochondrial dysfunction.