title: Damaged mitochondria and overproduction of ROS in Fanconi anemia cells.
abstract: Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents. To date, 15 different genes have been shown to cause FA, all of which have some role in repair of defective DNA interstrand crosslinks. On a biochemical level, many FA individuals display insufficient growth hormone production, abnormal glucose or insulin metabolism. Clinical phenotype may include hydrocephalia, the erythrophagocytosis and diabetes mellitus, thus linking FA with metabolic disorders that involve impaired oxygen metabolism and mitochondrial alterations. Our recent study demonstrates the decrease of FA mitochondrial membrane potential, low ATP production, impaired oxygen uptake and pathological changes in the morphology of FA mitochondria. This is accompanied by inactivation of the enzymes responsible for energy production and detoxification of ROS. We also propose that FA oversensitivity to DNA crosslinkers may be caused by the overproduction of mitochondrial ROS.
authors.affiliation: Cancer and Stem Cell Research Program; DUKE-NUS Graduate Medical School; Singapore, Singapore.
authors.forename: Alex
authors.initials: A
authors.lastname: Lyakhovich
keywords: Fanconi anemia; ROS; metabolic disorders; mitochondria; oxidative stress