Mitochondrial stress triggers ELT-2-controlled cell recycling to extend lifespan in C. elegans

Inhibition of mitochondrial respiration enhances lysosomal proteolysis and may extend lifespan in Caenorhabditis elegans.

• Mild mitochondrial stress is associated with a sustained transcriptional program that improves lysosomal function during aging.
• The intestinal GATA transcription factor ELT-2 plays a crucial role in regulating this response by promoting the expression of lysosomal protease genes.
• A specific residue, R249, within the DNA binding domain of ELT-2 is necessary for its transcriptional activity.
• The ELT-2-dependent lysosomal pathway operates largely independently of the mitochondrial unfolded protein response (UPR^mt).
• Increased activity of lysosomal proteases, including CPR-5 and CPR-8, is essential for clearing toxic polyglutamine aggregates and supporting lifespan extension.

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