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Differential Proteomics of Ptl-1 KO and Control C.elegans

ABSTRACT: Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations are known to impair mitochondrial dynamics and function, the physiological role of wild-type Tau in the maintenance of mitochondrial homeostasis remains poorly understood. Here, using C. elegans and mice lacking PTL-1, the nematode Tau-like homolog, and Tau respectively, we demonstrate that Tau deficiency enhances mitochondrial respiration, ATP production and mitophagy, promoting a pro-fusion mitochondrial network in neurons. Tau-deficient nematodes also display increased resistance to stressors, including heat and mitochondrial insults. Strikingly, loss of FZO-1, the mitofusin homolog, abolishes these effects, reducing mitochondrial function and stress resistance in PTL-1 deficient nematodes. Our findings reveal a conserved role for wild-type Tau in restraining mitochondrial fusion and activity via mitofusins, highlighting its contribution to mitochondrial quality control and cellular stress resilience.

INSTRUMENT(S):

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

SUBMITTER: Martina Samiotaki

LAB HEAD: Konstantinos Palikaras

PROVIDER: PXD073360 | Pride | 2026-06-15

REPOSITORIES: Pride

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