The peroxin Pex14p is involved in LC3-dependent degradation of mammalian peroxisomes
The peroxin Pex14p is involved in LC3-dependent degradation of mammalian peroxisomes
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DOI：
10.1016/j.yexcr.2008.09.015
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发表时间：
2008-11-15
影响因子：
3.7
通讯作者：
Fujiki, Yukio
中科院分区：
文献类型：
--
作者：
Hara-Kuge, Sayuri;Fujiki, Yukio
为了进一步了解哺乳动物细胞中过氧化物酶体的动态平衡，我们研究了中国仓鼠卵巢（CHO）-K1细胞中过氧化物酶体在营养饥饿下的降解系统。当CHO-K1细胞在Hank's溶液中饥饿，然后在正常培养基中再培养时，过氧化物酶体蛋白以明显优于胞质蛋白的方式降解。我们验证了微管相关蛋白I轻链3（LC 3），一个必不可少的因素，自噬，是否参与过氧化物酶体蛋白的降解。在LC 3敲低的CHO-K1细胞中，不再观察到过氧化物酶体蛋白的特异性降解，并且在饥饿条件下，包括过氧化物酶体和胞质蛋白在内的蛋白质被非选择性地降解。蛋白酶体抑制剂MG 132和Epoxomicin可抑制饥饿依赖的非选择性蛋白质降解。在饥饿条件下，完整的膜peroxin，Pex 14 p与膜结合的LC 3-II，LC 3的修饰形式，通过微管相互作用。两者合计，这些结果表明，过氧化物酶体蛋白降解的两个降解系统，涉及自噬和蛋白酶体取决于各种细胞培养条件，和Pex 14 p起着关键作用，作为一个先决条件的因素，过氧化物酶体蛋白降解的自噬与微管的帮助。(C)2008年爱思唯尔公司All rights reserved.
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. (C) 2008 Elsevier Inc. All rights reserved.