Fig. 3.

The Lon protease and aging-related changes. (A, C) During periods of acute oxidative stress, peroxisomes and mitochondria quickly adapt to the oxidative insult by up-regulating LonP1 and LonP2. (A) In young mitochondria, the resulting increase in proteolytic activity of LonP1 ensures rapid degradation of damaged proteins and maintenance of homeostasis. (B) Young peroxisomes adapt to changes in metabolic demand by rapidly increasing the breakdown of odd-chain fatty acids for increased acetyl-CoA production, which consequently fuels mitochondrial energy production. To compensate for the excess generation of hydrogen peroxide, up-regulation of LonP2 counteracts the increased peroxisome-dependent protein damage. (B, D) Senescent cells that are exposed to chronic oxidative stress lose ability to degrade oxidized organelle proteins. (B) In aged mitochondria, the ability to rapidly up-regulate LonP1 declines, leading to the accumulation of protein aggregates, and eventual loss of mitochondrial function. (D) In peroxisomes, a similar phenomenon may occur, in which the decreased ability to elevate LonP2 levels rapidly could also lead to protein aggregation and the gradual loss of peroxisome function.