The peroxin Pex14p is involved in LC3-dependent degradation of mammalian peroxisomes.

As a step toward understanding the homeostasis of peroxisomes in mammalian cells, we investigated a degradation system of peroxisomes in Chinese hamster ovary (CHO)-K1 cells in response to the nutrient-starvation. Peroxisomal proteins were degraded apparently in a preferential manner as compared to cytosolic proteins, when CHO-K1 cells were starved in Hank's solution and then re-cultured in a normal medium. We verified whether microtubule-associated protein I light chain 3 (LC3), an essential factor for autophagy, was involved in the degradation of peroxisomal proteins. In the LC3-knocked-down CHO-K1 cells, the specific degradation of peroxisomal proteins was no longer observed and proteins including peroxisomal and cytosolic proteins were rather non-selectively degraded under the starvation condition. The starvation-dependent non-selective protein degradation was inhibited with proteasome inhibitors, MG132 and Epoxomicin. The integral membrane peroxin, Pex14p interacted with membrane-bound LC3-II, the modified form of LC3, via microtubules under the starvation condition. Taken together, these results suggest that peroxisomal proteins are degraded by two degradation systems involving autophagy and proteasomes depending on various cell-culture conditions, and that Pex14p plays a pivotal role as a prerequisite factor for the degradation of peroxisomal proteins by autophagy with the aid of microtubules.