ArticleRedox biology2026
Excessive ER-mitochondria coupling: A DRP1-driven mechanism underlying mitochondrial dysfunction and impaired autophagy in stress-induced depression-like behavior in mice.
Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Remodeling of the mitochondrial quality control network: natural products intervening in diabetic retinopathy.Frontiers in pharmacology · 2026Review
- Mitochondria-ER contact sites in neurological disorders.Animal cells and systems · 2026Review
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDepression is a common psychiatric disorder characterized by heightened stress exposure and disruptions in neuronal signaling. Growing evidence suggests that mitochondrial dysfunction contributes to its pathophysiology. In particular, mitochondrial dynamics regulated by Dnm1l/Drp1 are critical for neuronal homeostasis, and their dysregulation may lead to cellular impairment. Additionally, mitochondrial-endoplasmic reticulum contact sites (MERCs) are crucial for maintaining cellular function and require precise regulation. However, the role of Drp1 in modulating MERC structure and function in the context of depression remains unclear.
methodsWe quantified protein changes via 4D-FastDIA proteomics. MERC alterations were examined using transmission electron microscopy (TEM) and proximity ligation assay (PLA). Mitochondrial metabolism was assessed with the Seahorse XF Analyzer. Autophagy was visualized through tyramine signal amplification and Imaris-based 3D reconstruction. The causal relationship was tested using Vglut2-Cre mice combined with specific flox-virus mediated Drp1 manipulation and pharmacological inhibition of autophagy. Depression-like behaviors were evaluated after chronic social defeat stress (CSDS).
resultsDrp1 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. These findings identify Drp1-mediated MERC disruption as a key mechanism in depression and suggest therapeutic strategies targeting MERC integrity and autophagy.
conclusionOur results provide novel mechanistic evidence that Drp1-mediated dysfunction at MERCs and impaired mitochondrial quality control contribute to the pathogenesis of depression. These findings underscore the importance of endoplasmic reticulum-mitochondrial crosstalk in depression and suggest potential therapeutic targets for modulating cellular resilience in stress-related disorders.
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