Full-length TDP-43 and its C-terminal fragments activate mitophagy in NSC34 cell line.

TAR DNA binding protein of 43kDa (TDP-43), which has been associated with amyotrophic lateral sclerosis (ALS), plays an essential role in neurodegenerative disease pathogenesis. In particular, mitochondrial dysfunction is involved in the disease development. Thus, we investigated how TDP-43 is related to mitochondrial dysfunction. In this study, we found that overexpression of TDP-43 and its C-terminal fragments resulted in mitochondrial damage. In addition, full-length TDP-43 and truncated TDP-43 were localized in the mitochondria, where autophagy was activated, indicated by changes of LC3-II and p62. These studies suggest that human TDP-43 and its C-terminal fragments may cause mitochondrial dysfunction and enhance mitophagy.