Mitochondrial Endonuclease G function in apoptosis and mtDNA metabolism: a historical perspective

All mitochondria contain a single, major Mg2+-dependent nuclease capable of extensively degrading DNA and RNA in vitro. This nuclease activity and its gene now go by the name Endonuclease G. For many years, however, a number of different names for this mitochondrial nuclease have been used. This can lead to great deal of confusion for anyone searching the literature. The name Endonuclease G had originally been assigned to an endonuclease activity identified in nuclear extracts of chicken erythrocytes that was found to specifically nick within guanine (G) tracts in DNA in vitro. Subsequent studies however, established that this Endonuclease G activity was identical to the well known, major endonuclease activity isolated from mitochondria of several species. In addition, studies of the mammalian mitochondrial endonuclease showed that the endonuclease is not restricted to only attacking guanine tracts, although it does so avidly. The enzyme is also capable of avidly nicking within cytosine tracts, and at a large variety of sites, that fragments duplex DNA extensively. Despite this, the name Endonuclease G persists. One purpose of this review is to summarize the history of Endonuclease G that spans some 40 years, and review what we have learned about the enzyme's biochemical and biologic properties. Endonuclease G likely serves a role in repair and/or degradation of damaged mtDNA in vivo. Recently, genetic and biochemical evidence has emerged that Endonuclease G is released from the inter membrane space during early stages of programmed cell death, and translocates to the nucleus where it presumably facilitates degradation of chromatin. This exciting new potential role for the enzyme in apoptotic cell death will be discussed.