Endoplasmic Reticulum Regulation of Mitochondrial DNA Replication

Mitochondrial function is reliant on interactions with other cell compartments, particularly the endoplasmic reticulum, via endoplasmic reticulum-mitochondrial contact sites (ERMCS). This thesis aims to elucidate how the ER influences mitochondrial DNA (mtDNA) replication, an essential process for cellular energy production and survival. It reveals that mtDNA replication is proportional to ERMCS abundance. It highlights the influence of nutrients, particularly glutamine, and cell division on mtDNA replication, which suggest the ER coordinates nuclear and mitochondrial replication via membrane contact sites. And, finally, it proposes manganese as a key replication-stimulator factor of mtDNA replication, transported via the mitochondrial calcium uniporter and regulated by superoxide dismutase 2. This research sheds light on the intricate mechanisms of ER-mitochondria communication that are heavily implicated in neurological disorders, and offers a potential therapeutic approach for stimulating mtDNA replication when ERMCS are dysfunctional.