Can folic acid have a role in mitochondrial disorders?

•Folate metabolism in the cell is highly compartmentalized.•There are evidences of the importance of folate regarding mitochondrial function.•Cerebral folate deficiency is frequent in certain mitochondrial disorders.•Folate treatment has positive effects in patients with mitochondrial DNA deletions. Cellular folate metabolism is highly compartmentalized, with mitochondria folate transport and metabolism being distinct from the well-known cytosolic folate metabolism. There is evidence supporting the association between low folate status and mitochondrial DNA (mtDNA) instability, and cerebral folate deficiency is relatively frequent in mitochondrial disorders. Furthermore, folinic acid supplementation has been reported to be beneficial not only in some patients with mitochondrial disease, but also in patients with relatively common diseases where folate deficiency might be an important pathophysiological factor. In this review, we focus on the evidence that supports the potential involvement of impaired folate metabolism in the pathophysiology of mitochondrial disorders.