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Epithelial-to-mesenchymal transition (EMT) is critical to several pathological processes including carcinoma metastasis and organ fibrosis, involving with altered mitochondria status. However, little is known about the relationship between mitochondrial function and EMT. In current study, we demonstrated that EMT impairs mitochondrial biogenesis, as evidenced by decreased mitochondrial DNA content and downregulation of PGC-1α, NRF-1, TFAM and upstream regulator SIRT1 following treatment with TGF-β1. EMT also impaired mitochondrial function by increasing ROS production and reducing mitochondrial membrane potential, ATP content and mitochondrial complex protein expression. Resveratrol, an activator of the SIRT1 pathway rescued EMT mediated mitochondrial dysfunction and biogenesis impairment, as well as inhibited EMT process. However, resveratrol is not sufficient to reverse EMT in a mitochondrial dysfunction model. These findings suggest a critical role for mitochondrial functions in EMT and implicate the SIRT1/PGC-1a pathway as a potential target to prevent EMT to treat tumor metastasis and fibrosis, and other diseases related to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]