Old mitochondria accumulate in pachyonychia congenita
Old mitochondria accumulate in pachyonychia congenita
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先天性厚甲症中老线粒体积聚
DOI：
10.1111/bjd.18465
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发表时间：
2020
影响因子：
10.3
通讯作者：
Magin TM
中科院分区：
文献类型：
--
作者：
Vetter A;Magin TM
表皮稳态是自我更新和分化周期的结果，干细胞在此过程中分化为未成熟的角质形成细胞。这些细胞的主要结构元素是由角蛋白组成的中间丝（IF），根据其初级氨基酸序列区分为I型和II型。角蛋白(K)基因K6a、K6b、K16和K17的突变导致罕见的先天性厚甲病（PC），其特征为肥厚性指甲营养不良和疼痛性掌跖角化病。1,2角化过度也可能由线粒体ROS信号传导缺陷引起，这可能通过WNT-bcatenin和Notch信号传导损害角化细胞分化。新出现的证据表明，IF蛋白在线粒体功能和多种机制的信号传导中发挥重要作用。例如，III型IF蛋白波形蛋白被证明可以调节线粒体运动和细胞内定位，而小鼠皮肤中角蛋白丝的完全缺失改变了线粒体的蛋白质和脂质组成，增加了线粒体的耗氧量。考虑到表皮中PC和线粒体活性缺陷的相似性，Lehmann及其同事研究了PC相关的K6a突变在线粒体质量控制和清除中的作用，并在本期的《英国医学杂志》上发表了他们的研究结果。7
Epidermal homeostasis results from cycles of self-renewal and differentiation, during which stem cells differentiate into immature keratinocytes. A major structural element in these cells are intermediate filaments (IF) made from keratins, from which two groups called type I and II are distinguished based on their primary amino acid sequence. Mutations in keratin (K) genes K6a, K6b, K16 and K17 cause the rare skin disease pachyonychia congenita (PC), characterized by hypertrophic nail dystrophy and painful palmoplantar keratoderma. 1, 2 Hyperkeratosis can also result from defective mitochondrial ROS signalling which impairs keratinocyte differentiation, possibly through WNT–bcatenin and Notch signalling. 3Emerging evidence suggests a vital role for IF proteins in mitochondrial function and signalling through diverse mechanisms. 4 The type III IF protein vimentin, for example, was shown to modulate mitochondrial motility and intracellular localization, 5 whereas the complete absence of keratin filaments in mouse skin altered protein and lipid composition of mitochondria and increased mitochondrial oxygen consumption. 6 Considering the similarity of PC and defective mitochondrial activity in the epidermis, Lehmann and colleagues investigated the role of PC-associated K6a mutations in mitochondrial quality control and clearance, and present their findings in this issue of the BJD. 7
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