The activation of part of a nutritional signaling pathway clears protein aggregates, as shown by Yamamoto et al. (page 719). The findings suggest that cells in crisis get an unusual outcome from insulin pathways.
Insulin signaling tells the cell that energy sources are present. It thus turns on protein translation and inactivates autophagy, which degrades bulk cytoplasmic proteins to supply starving cells with amino acids. The autophagy is turned on when insulin signaling activates an insulin receptor effector, called IRS-2, which then turns on a PI3K.
Yamamoto et al. found that aggregates of mutant huntingtin protein (htt) also turned on IRS-2, but that this increased autophagy. Insulin-activated and htt-activated IRS-2 had different activities because the latter activated a different PI3K, called hVps34, to clear htt aggregates via autophagy and lysosomal degradation. Thus, the insulin pathway, which is thought to convey a state of well-being,...
