Tau Protein Disrupts Mitochondrial Homeostasis in a Yeast Model: Implications for Alzheimer's Disease.

ABSTRACT: The microtubule-associated protein tau plays a central role in neurodegenerative diseases, called tauopathies, but the mechanism involved remains incompletely understood. Here, we used Saccharomyces cerevisiae as a model system to investigate the consequences of expressing the shortest human tau isoform 0N3R. After transfected, we detected widespread cellular distribution of tau and phosphorylation at key pathological residues involved in Alzheimer's disease (Ser199/202). We also found that a portion of tau localizes within the mitochondrial matrix. The mitochondrial uptake of tau required a chaperone machinery, including Hsp104 and the Ssa1/Ydj1 bichaperone complex. Functionally, tau expression caused marked mitochondrial fragmentation, reduced oxygen consumption, and a decrease in membra

SUBMITTER: Castillo-Casana Y 

PROVIDER: S-EPMC12559152 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature