Background: Mitochondrial aconitase (Aco2), a member of the family of iron-sulfur [4Fe-
4S]-containing dehydratases, is involved in cellular metabolism through the tricarboxylic acid cycle.
Aco2 is highly susceptible to oxidative damage in a way that exposure to the reactive species and free
radicals leads to release of iron from the central [4Fe-4S] cluster resulting in the production of the inactive
form of Aco2.
Objective: There is increasing evidence supporting a direct association between impaired energy metabolism
and the incidence and progression of neurodegenerative disorders in neuronal cells.
Results: It has been shown that alteration in bioenergetic parameters is a common pathological feature
of the neurodegenerative diseases leading to neuronal dysfunction. Numerous studies have demonstrated
that dysfunctional Aco2, among the other bioenergetic parameters, is a key factor that could
Conclusion: Increasing our knowledge about energy metabolism-related molecules including Aco2
affected by neurodegenerative disorders might be useful to find an efficient therapeutic strategy for
those central nervous system-related diseases. Accordingly, in this review, we have focused on the
events and processes that occur in neurodegeneration, leading to the inactivation of Aco2 in the brain.