Mechanisms regulating mitochondrial DNA quality control

Maintenance of genome integrity is essential for cellular survival. There are mechanisms utilized by the cells to sense and respond to assaults on genomic DNA. These mechanisms are conserved across all domains of life and are collectively called the DNA damage response pathways. However, eukaryotic cells also have extrachromosomal DNA in mitochondria (mtDNA), which is indispensable for mitochondrial function, and hence cell survival. Indeed, impaired mitochondrial activity arising due to mutations in mtDNA has been found to be associated with many human pathologies. Despite its importance, our understanding of how cells ensure mtDNA genome integrity is limited. Since mitochondria do not encode for machinery required for the maintenance of their own genomes, they depend on the nucleus for replication, transcription, and repair processes. This adds a layer of complexity with the requirement for organelle crosstalk and coordination in response to mtDNA damage. This review summarizes recent findings that provide new insights into mechanisms involved in mtDNA quality control, acting at the level of mtDNA or organelle and also discusses a few new avenues of research towards a comprehensive understanding of the “mtDNA damage response”.