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Mitochondrial dysfunction and oxidative stress are major contributors to the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the mechanisms driving mitochondrial dysfunction and oxidative stress are unclear. Familial AD (fAD) is an early onset form of AD caused primarily by mutations in the presenilin-encoding genes. Previously, using <i>Caenorhabditis elegans</i> as a model system to study presenilin function, we found that loss of <i>C. elegans</i> presenilin orthologue SEL-12 results in elevated mitochondrial and cytosolic calcium levels. Here, we provide evidence that elevated neuronal mitochondrial generated reactive oxygen species (ROS) and subsequent neurodegeneration in <i>sel-12</i> mutants are a consequence of the increase of mitochondrial calcium levels and not cytosolic calcium levels. We also identify mTORC1 signaling as a critical factor in sustaining high ROS in <i>sel-12</i> mutants in part through its repression of the ROS scavenging system SKN-1/Nrf. Our study reveals that SEL-12/presenilin loss disrupts neuronal ROS homeostasis by increasing mitochondrial ROS generation and elevating mTORC1 signaling, which exacerbates this imbalance by suppressing SKN-1/Nrf antioxidant activity.