Endoplasmic reticulum-mitochondrial crosstalk in depression

Stress exposure may lead to disruptions in neuronal signaling leading to depression.  Mitochondrial function regulated by Dnm1l/Drp1 become dysfunctional during depression.

Mitochondrial-endoplasmic reticulum contact sites (MERCs) are important for neuronal function but the role of Drp1 in regulating MERCs in depression is unclear.

The authors show that Drp1 activation disrupts mitochondrial-endoplasmic reticulum contact sites (MERCs), leading to mitochondrial dysfunction and impaired autophagy, and ultimately promoting depressive-like behaviors.

Inhibiting the MERC tethering protein GRP75 or enhancing mitophagy pharmacologically alleviated these neuronal and behavioral deficits.

This study identifies Drp1-mediated MERC disruption as a key mechanism in depression and suggest therapeutic strategies targeting MERC integrity and autophagy.

https://www.sciencedirect.com/science/article/pii/S2213231726001199

https://sciencemission.com/ER-mitochondria-coupling