Key result
Cardiomyocyte Tau overexpression drives cardiac hypertrophy via mitochondrial fission, attenuated by Mdivi-1 inhibition.
Why the study?
The role of Tau in cardiac pathophysiology remained elusive despite evidence of its cardiac expression.
Tau overexpression promotes cardiac hypertrophy and heart failure by disrupting mitochondrial dynamics, identifying it as a potential therapeutic target for cardiac remodeling.
Answers are grounded in this paper and cite their sources.
Tau may drive hypertrophy via fission in mice; leaves open whether targeting it or DRP1 alters human heart failure progression.
Tau is classically defined as a microtubule-associated protein whose dysfunction underpins neurodegenerative disorders. However, its role in cardiac pathophysiology remains elusive despite recent evidence of its cardiac expression. Here, we report that a ~55 kDa Tau-immunoreactive species, which is commonly found in the nervous system, is markedly upregulated in isoproterenol-induced hypertrophic murine hearts, suggesting that this stress-inducible species is associated with maladaptive cardiac remodeling. Forced Tau expression was sufficient to induce hypertrophic growth in cultured cardiomyocytes. Cardiomyocyte-restricted Tau overexpression in transgenic mice recapitulated the progressive trajectory from hypertrophy to overt heart failure. Mechanistically, Tau overexpression triggered excessive mitochondrial fission, leading to mitochondrial dysfunction evidenced by reduced mitochondrial membrane potential, elevated reactive oxygen species, diminished activity of respiratory chain complexes I and IV, and decreased intracellular ATP. Pharmacological inhibition of mitochondrial fission with Mdivi-1 attenuated Tau overexpression-induced cardiomyocyte hypertrophy; taken together, our gain-of-function evidence identifies the ~55 kDa Tau-immunoreactive species as a stress-associated factor that disrupts mitochondrial dynamics to promote cardiac remodeling, and suggests Tau as a potential therapeutic target for cardiac diseases.
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Xu et al. (2026) studied Cardiac hypertrophy and heart failure. Tau overexpression vs. Wild-type littermates or Ad-GFP control was evaluated on Cardiac hypertrophy and mitochondrial dysfunction. Cardiomyocyte-specific Tau overexpression induced progressive cardiac hypertrophy and heart failure by triggering excessive mitochondrial fission, which was attenuated by pharmacological inhibition with Mdivi-1.
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