Extended Data Figure 7. Proposed model.

Scheme illustrating the role of mitochondrial proteostasis in Aβ proteopathies based on our studies in the GMC101 model. (1) Accumulation of amyloid aggregates triggers mitochondrial dysfunction, which induces the MSR. (2) atfs-1 depletion results in loss of mitochondrial homeostasis, more pronounced amyloid aggregation and decreased healthspan. (3) Enhancing mitochondrial proteostasis with dox, mrps-5 RNAi, and NAD⁺ boosters (NR and Olaparib), increases organismal fitness, delaying the development of Aβ proteotoxicity.