COPI-regulated mitochondria-ER contact site formation maintains axonal integrity.

ABSTRACT: Coat protein complex I (COPI) is best known for its role in Golgi-endoplasmic reticulum (ER) trafficking, responsible for the retrograde transport of ER-resident proteins. The ER is crucial to neuronal function, regulating Ca²⁺ homeostasis and the distribution and function of other organelles such as endosomes, peroxisomes, and mitochondria via functional contact sites. Here we demonstrate that disruption of COPI results in mitochondrial dysfunction in Drosophila axons and human cells. The ER network is also disrupted, and the neurons undergo rapid degeneration. We demonstrate that mitochondria-ER contact sites (MERCS) are decreased in COPI-deficient axons, leading to Ca²⁺ dysregulation, heightened mitophagy, and a decrease in respiratory capacity. Reintroducing MERCS

SUBMITTER: Maddison DC 

PROVIDER: S-EPMC10840514 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature