The interplay between mitochondrial functionality and genome integrity in the prevention of human neurologic diseases

As mitochondria are vulnerable to oxidative damage and represent the main source of reactive oxygen species (ROS), they are considered key tuners of ROS metabolism and buffering, whose dysfunction can progressively impact neuronal networks and disease. Defects in DNA repair and DNA damage response (DDR) may also affect neuronal health and lead to neuropathology. A number of congenital DNA repair and DDR defective syndromes, indeed, show neurological phenotypes, and a growing body of evidence indicate that defects in the mechanisms that control genome stability in neurons acts as aging-related modifiers of common neurodegenerative diseases such as Alzheimer, Parkinson's, Huntington diseases and Amyotrophic Lateral Sclerosis. In this review we elaborate on the established principles and recent concepts supporting the hypothesis that deficiencies in either DNA repair or DDR might contribute to neurodegeneration via mechanisms involving mitochondrial dysfunction/deranged metabolism.

Automated summary

Mitochondria are vulnerable to oxidative damage and play a key role in ROS metabolism, impacting neuronal networks and disease progression; Defects in DNA repair and DDR can also affect neuronal health and lead to neurological symptoms; Dysfunction in mechanisms controlling genome stability in neurons may contribute to common neurodegenerative diseases via involving mitochondrial dysfunction and altered metabolism.