Mitochondrial dysfunction in human TDP-43 transfected NSC34 cell lines and the protective effect of dimethoxy...

TAR-DNA-binding protein of 43kDa (TDP-43) was recently found to be one of the major disease proteins in the pathological inclusions of amyotrophic lateral sclerosis (ALS). The effect of TDP-43 on mitochondrial function remains poorly understood. Here, we show that human TDP-43 caused mitochondrial morphologic abnormality, decrease of mitochondrial complex I activity and mitochondrial transmembrane potential, and increased expression of mitochondrial uncoupling protein 2 (UCP2) in human TDP-43 stably transfected NSC-34 cells by using flow cytometric analysis, spectrophotometric assays, electron microscopy and Western blotting. We also show that dimethoxy curcumin (DMC) could ameliorate mitochondrial dysfunction in mutated TDP-43 stably transfected cell lines. DMC could be potentially useful for neurodegenerative diseases linked with mutated TDP-43.