Running in reverse: Tau redirects mitochondrial electron flow toward neurodegeneration.

Tau enters mitochondria and binds NDUFS3 to regulate reverse electron transport, promoting tau phosphorylation in a phosphorylation-dependent manner.

• Why it matters: Understanding how tau influences mitochondrial function is crucial because it may reveal mechanisms underlying tauopathies and neurodegeneration.
• What they did: Li et al. used biochemical and cellular approaches to demonstrate that tau interacts with NDUFS3 within mitochondria, affecting RET and tau phosphorylation in a phosphorylation-dependent manner.
• The result: The findings suggest a self-perpetuating loop where RET promotes tau phosphorylation, which may exacerbate neurodegeneration under stress and tauopathy conditions.