Temporal Interactome Mapping of Human Tau in Drosophila Reveals Progressive Mitochondrial Engagement and Porin/VDAC1-Dependent Modulation of Toxicity.

ABSTRACT: Tau protein misfolding and aggregation are central to Tauopathies, yet the temporal dynamics of Tau interactions in vivo remain poorly understood. Here, we applied quantitative proteomics to demonstrate that the interactome of human Tau in adult Drosophila brains changes dynamically over a 12-day time course, revealing a progressive shift from early cytosolic and ribosomal associations to late enrichment of mitochondrial and synaptic partners. Notably, the mitochondrial pore protein Porin/VDAC1 was identified as a late-stage interactor and functional analyses demonstrated that Tau overexpression impairs mitochondrial respiration, elevates oxidative damage, and disrupts carbohydrate homeostasis. To validate this temporally specific interaction, Porin was downregulated, resulting in reduced

SUBMITTER: Tsakiri E 

PROVIDER: S-EPMC12524354 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature