Docosahexaenoic acid mediates peroxisomal elongation, a prerequisite for peroxisome division
Docosahexaenoic acid mediates peroxisomal elongation, a prerequisite for peroxisome division
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DOI：
10.1242/jcs.087452
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Fujiki, Yukio
中科院分区：
文献类型：
--
作者：
Itoyama, Akinori;Honsho, Masanori;Fujiki, Yukio
过氧化物酶体分裂受多种因素（称为裂变因子）以及细胞环境条件的调节。在过去的十年中，人们提出了过氧化物酶体形态发生的代谢控制的想法，但迄今为止仍然很大程度上未得到定义。在当前的研究中，二十二碳六烯酸（DHA，C22:6n-3）被确定为过氧化物酶体分裂的诱导剂。在从具有过氧化物酶体脂肪酸β-氧化缺陷的患者中分离的成纤维细胞中，过氧化物酶体的丰度远低于正常细胞。用 DHA 治疗这些患者成纤维细胞可诱导过氧化物酶体增殖至正常成纤维细胞的水平。通过使用靶向动力样蛋白 1 的小抑制性 RNA (siRNA) 和动力样蛋白 1 的抑制剂 dynasore 处理，DHA 诱导的过氧化物酶体增殖被消除，这表明 DHA 刺激过氧化物酶体分裂。 DHA 增强了 Pex11p β 的超寡聚化以及细长过氧化物酶体上 Pex11p β 富集区域的形成。过氧化物酶体形态发生的延时成像分析揭示了过氧化物酶体分裂涉及的一系列步骤，包括在一个方向上的伸长以及随后的过氧化物酶体裂变。 DHA 以不依赖微管的方式增强过氧化物酶体分裂。这些结果表明，DHA 是过氧化物酶体延伸的关键信号，是随后裂变和过氧化物酶体分裂的先决条件。
Peroxisome division is regulated by several factors, termed fission factors, as well as the conditions of the cellular environment. Over the past decade, the idea of metabolic control of peroxisomal morphogenesis has been postulated, but remains largely undefined to date. In the current study, docosahexaenoic acid (DHA, C22:6n-3) was identified as an inducer of peroxisome division. In fibroblasts isolated from patients that carry defects in peroxisomal fatty acid beta-oxidation, peroxisomes are much less abundant than normal cells. Treatment of these patient fibroblasts with DHA induced the proliferation of peroxisomes to the level seen in normal fibroblasts. DHA-induced peroxisomal proliferation was abrogated by treatment with a small inhibitory RNA (siRNA) targeting dynamin-like protein 1 and with dynasore, an inhibitor of dynamin-like protein 1, which suggested that DHA stimulates peroxisome division. DHA augmented the hyperoligomerization of Pex11p beta and the formation of Pex11p beta-enriched regions on elongated peroxisomes. Time-lapse imaging analysis of peroxisomal morphogenesis revealed a sequence of steps involved in peroxisome division, including elongation in one direction followed by peroxisomal fission. DHA enhanced peroxisomal division in a microtubule-independent manner. These results suggest that DHA is a crucial signal for peroxisomal elongation, a prerequisite for subsequent fission and peroxisome division.