Figure 4. Mitochondrial stress and lifespan regulation.

(A) Lifespan increases with moderate levels of mitochondrial dysfunction and is reduced when the damage is too severe. During mild mitochondrial dysfunction (orange), which may affect the entire mitochondrial pool or individuals organelles, the organism is able to promote mitochondrial recovery through physiological alterations that positively affect lifespan. These adaptations include pro-survival metabolic alterations, maintenance of the mitochondrial protein folding environment and resistance to pathogens. (B) The UPR^mt is activated in response to mitochondrial dysfunction and promotes mitochondrial repair and metabolic adaptations. At some point, the mitochondrial damage becomes irreparable offsetting the UPR^mt-mediated protective effects (dashed line). During severe mitochondrial dysfunction UPR^mt activation still occurs, but may not be sufficient to maintain mitochondrial homeostasis and protect survival.