Decreasing pdzd8-mediated mito-ER contacts improves organismal fitness and mitigates Aβ₄₂ toxicity.

ABSTRACT: Mitochondria-ER contact sites (MERCs) orchestrate many important cellular functions including regulating mitochondrial quality control through mitophagy and mediating mitochondrial calcium uptake. Here, we identify and functionally characterize the Drosophila ortholog of the recently identified mammalian MERC protein, Pdzd8. We find that reducing pdzd8-mediated MERCs in neurons slows age-associated decline in locomotor activity and increases lifespan in Drosophila. The protective effects of pdzd8 knockdown in neurons correlate with an increase in mitophagy, suggesting that increased mitochondrial turnover may support healthy aging of neurons. In contrast, increasing MERCs by expressing a constitutive, synthetic ER-mitochondria tether disrupts mitochondrial transport and synapse formation,

SUBMITTER: Hewitt VL 

PROVIDER: S-EPMC9279675 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature