KRT8 (keratin 8) attenuates necrotic cell death by facilitating mitochondrial fission-mediated mitophagy through interaction with PLEC (plectin)
KRT8 (keratin 8) attenuates necrotic cell death by facilitating mitochondrial fission-mediated mitophagy through interaction with PLEC (plectin)
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DOI：
10.1080/15548627.2021.1897962
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发表时间：
2021-03-31
期刊：
影响因子：
13.3
通讯作者：
Kim, Dong-Eun
中科院分区：
文献类型：
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作者：
Baek, Ahruem;Son, Sumin;Kim, Dong-Eun
线粒体稳态的失调和受损线粒体的积累导致退行性疾病，如年龄相关性黄斑变性（AMD）。我们研究了中间细胞丝KRT8（角蛋白8）对线粒体稳态的影响，与氧化应激下视网膜色素上皮细胞线粒体的形态和功能有关。当线粒体由于氧化应激而受损时，受损的线粒体容易通过线粒体分裂后的线粒体自噬而被处置。在此过程中，发现KRT8通过PLEC（plectin）与线粒体物理相互作用，并促进线粒体分裂介导的线粒体自噬。然而，PLEC锚定线粒体和KRT8之间的关联减少了KRT8磷酸化氧化应激下。有效的KRT8促进的线粒体自噬通量抑制了受损线粒体的积累，从而减少了氧化应激下的坏死细胞死亡。因此，通过促进线粒体自噬，KRT8保护RPE细胞免受由于氧化应激引起的坏死性细胞死亡。
Dysregulation of mitochondrial homeostasis and accumulation of damaged mitochondria cause degenerative diseases such as age-related macular degeneration (AMD). We studied the effects of the intermediate cytofilament KRT8 (keratin 8) on mitochondrial homeostasis in relation to the morphology and function of mitochondria in retinal pigment epithelial cells under oxidative stress. When the mitochondria were damaged owing to oxidative stress, the damaged mitochondria were readily disposed of via mitophagy following mitochondrial fission. During this process, KRT8 was found to physically interact with the mitochondria through PLEC (plectin) and facilitate the mitochondrial fission-mediated mitophagy. However, the association between PLEC-anchoring mitochondria and KRT8 was dwindled by KRT8 phosphorylation under oxidative stress. The efficient KRT8-facilitated mitophagy flux suppressed the accumulation of damaged mitochondria and consequently diminished necrotic cell death under oxidative stress. Thus, by facilitating mitophagy, KRT8 protects RPE cells against necrotic cell death due to oxidative stress.