Fig. 1

The balance of TDP-43, mitochondria, and autophagy/mitophagy. In the healthy state, TDP-43 promotes mitochondrial biogenesis, mitochondria provide energy for the process of autophagy, and autophagy clears abnormal TDP-43 and damaged mitochondria. In neurodegenerative diseases, TDP-43 aggregates abnormally, impairing mitochondria and autophagy. Due to the autophagy dysfunction, the accumulated TDP-43 aggregates and damaged mitochondria cannot be cleaned up normally, leading to neuronal death.