Figure 1.

Mitokines coordinate inter-tissue communication of mitochondrial stress in Caenorhabditis elegans. In C. elegans, neurons under mitochondrial stress secrete mitokines to activate the UPR^MT and promote mitochondrial fragmentation in the intestine and to elevate mtDNA levels in the germline. Intestinal cells experiencing mitochondrial stress protect animals from neurodegeneration via the action of unknown mitokines. Mitochondrial stress or proteostasis failure in the germline leads to the release of mitokines that trigger the UPR^MT and AMPK signaling, reducing mitochondrial content and promoting mitochondrial fragmentation in the intestine, while also promoting protein aggregation in the intestine and neurons.