Tardbp G376D mutation

1. Tardbp G376D mutation activates ER unfolded protein response in human cells.

   “In parallel, activation of the Endoplasmic Reticulum UPR (UPR ER ) was observed, indicating a coordinated engagement of cellular stress pathways.”

   Cellsdermal fibroblast

   Mitochondrial Quality Control Impairment Is a Hallmark of TDP-43G376D ALS Patient-Derived Fibroblasts · Antioxidants (Basel, Switzerland) · 22 Aug 2026

ER unfolded protein response →

1. Tardbp G376D mutation activates mitochondrial unfolded protein response in human cells.

   “Furthermore, TDP-43 G376D induces sustained activation of the mitochondrial Unfolded Protein Response (UPR mt ), consistent with persistent mitochondrial stress”

   Cellsdermal fibroblast

   Mitochondrial Quality Control Impairment Is a Hallmark of TDP-43G376D ALS Patient-Derived Fibroblasts · Antioxidants (Basel, Switzerland) · 22 Aug 2026

Mitochondrial unfolded protein response →

1. Tardbp G376D mutation increases mitochondrial DNA damage in human cells.

   “This was accompanied by pronounced disruption of mitochondrial cristae architecture and accumulation of mitochondrial DNA damage, indicating compromised mitochondrial genome integrity.”

   Cellsdermal fibroblast

   Mitochondrial Quality Control Impairment Is a Hallmark of TDP-43G376D ALS Patient-Derived Fibroblasts · Antioxidants (Basel, Switzerland) · 22 Aug 2026

Mitochondrial DNA damage →

1. Tardbp G376D mutation impairs mitophagy in human cells.

   “We show that TDP-43 G376D impairs mitophagic flux, as evidenced by reduced delivery of damaged mitochondria to lysosomes.”

   Cellsdermal fibroblast

   Mitochondrial Quality Control Impairment Is a Hallmark of TDP-43G376D ALS Patient-Derived Fibroblasts · Antioxidants (Basel, Switzerland) · 22 Aug 2026

Mitophagy →