A case for DNA-membrane interactions in the responses to DNA damage

Eukaryotic cells harbour two genomes, the nuclear and the mitochondrial ones. Both are subjected to spontaneous and induced DNA damage that threatens biological function. In the nucleus, damage in the DNA is detected, signalled and taken care of by a dedicated, complex network of proteins termed the DNA Damage Response (DDR). In the mitochondria, this first-front DNA damage detection network is less characterized, despite that effective, downstream mitochondrial DNA (mtDNA) repair is documented. Also, given that mtDNA exists as multiple copies inside a single mitochondrion, the cell can selectively get rid of unhealthy mtDNA molecules. This later process suggests the existence of an additional quality control mechanism operating within mitochondria. Careful analysis of the literature suggests that damaged DNA can cause alterations in surrounding membrane structure / composition that could be integrated as an output to appropriately respond to such DNA damage. In this review, I discuss the evidence for membranes' involvement in the response to mtDNA damage. Finally, I discuss similarities and differences between mitochondrial and nuclear membranes and further extend the hypothesis to the possibility that membranes may play roles in signalling DNA damage that arise in the nuclear genome.