Figure 6. Proposed models of mitochondrial responses to stress.

Two simple models by which mitochondria respond to insults that increase ATP demand. Model 1, “Balance the load” model: When the need for energy arises, mitochondria respond collectively to increase ATP. A moderate demand is matched by a commensurate change in the mitochondrial state_apparent to somewhere in the midrange (e.g., state 3.5). Upon a strong challenge, all mitochondria in the cell respond and increase respiration to near their maximal rate (e.g., state 3.1). Model 2, “Engage when needed” model: In this model, most mitochondria in cells with low ATP demand idle at a respiratory state near 4, and only a subset of mitochondria work at a respiratory state more toward 3 to uphold basal energy requirements. When a moderate demand for energy arises, the cell then engages other subsets of mitochondria to generate the required amount of ATP. Under these conditions, some mitochondria might be near state 3.9 while others are more near state 3.1, averaging a collective state_apparent of 3.5. During times of very high energy demand, more mitochondria engage, yet a subpopulation of mitochondria remains in a resting state.