The effect of nutrient deprivation on proteasome activity in 4-week-old mice and 24-week-old mice.

Recently, we have begun to better understand the regulatory mechanisms of proteasome activity in response to the nutritional state. In this study, we analyzed the expression and function of proteasomes in the livers and brains where changes in the metabolic system occur in vivo during short-term starvation. In the livers of 4-week-old mice, proteasome activity decreased with fasting time, whereas brain proteasome activity remained unchanged by up to 24 h of fasting and then decreased. However, liver and brain proteasome activity in 24-week-old mice decreased by fasting for 24 h and then recovered. There was no significant change in the expression levels of the subunits that make up the proteasomes in livers and brains regardless of age, and there was no change in the molecular size of the formed proteasome. Interestingly, Ump1, a proteasome assembly protein, accumulated with changes in proteasome activity. When the fasted state returned to a fed state, the proteasome activity in the brain was restored to almost the same level as in the fed state, but the proteasome activity in the liver was not restored to that of the fed state. In this state, the assembly protein Ump1 continued to accumulate. These findings suggest that (1) the expression of Ump1 is controlled by the nutritional state, and (2) the proteasome formation mechanism may differ depending on the organ.