受体介导的线粒体自噬
中文名称
通路描述
哺乳动物细胞中的线粒体自噬最初在胰高血糖素刺激的原代肝细胞中被观察到。哺乳动物细胞中线粒体自噬的机制尚不清楚。氧化应激和线粒体通透性转换孔（mPTP）参与了线粒体自噬的启动。受体介导的线粒体自噬将细胞分化信号和线粒体功能标志物与LC3和Atg32等支架蛋白联系起来，这些支架蛋白对于底物选择和自噬体形成至关重要。这些支架蛋白招募其他自噬蛋白形成自噬体，从而破坏和回收线粒体。线粒体自噬受体必须满足三个条件：1) 必须位于线粒体上；2) 在特定刺激下与LC3/ATG8相互作用；3) 具有共识序列W/F/YxxL/I，称为LIR基序。该四肽序列存在于几个重要的ATG8或LC3结合伙伴中，这些伙伴对于选择性自噬至关重要。FUNDC1介导的线粒体自噬在正常氧条件下，其LIR基序中Tyr 18位的磷酸化会被Src激酶抑制，从而抑制线粒体自噬。在缺氧刺激下，Src被抑制，Tyr 18位的FUNDC1被未知磷酸酶去磷酸化，导致FUNDC1与LC3-II的相互作用增加，从而选择性掺入并自噬清除线粒体。BNIP3L/NIX是外周线粒体膜蛋白，参与网织红细胞中线粒体的自噬周转，这是红细胞成熟所必需的过程。BNIP3 LIR基序两侧的丝氨酸残基17和24的磷酸化促进其与特定的LC3家族成员LC3B和GATE-16的结合，并增加线粒体的溶酶体破坏。
英文描述
Regulation of MITF-M-dependent genes involved in pigmentation Genes involved in pigmentation and melanocyte structure and organization were among the first identified targets of MITF. Expression of enzymes TYR, DCT and TYRP1, which work sequentially to eventually convert tyrosine into eumelanin and pheomelanin, is regulated in part by the binding of MITF to M-boxes in the promoters (Bentley et al, 1994; Bertolotto et al, 1998; Yavuzer et al, 1995; reviewed in Cheli et al, 2010; Goding and Arnheiter, 2019). MITF additionally regulates the expression of structural components of the melanosome such as MLANA, SLC24A5, SILV and GPR143, although direct binding and regulation has not been demonstrated in all cases (Du et al, 2003; Cortese et al, 2005; Schiaffino and Tacchetti, 2005; reviewed in Cheli et al, 2010; Goding and Arnheiter, 2019). Genes encoding RAB27A and MYO5A, which regulate the localization and trafficking of melanosomes, are also targets of MITF (Chiaverini et al, 2008; Alves et al, 2017; reviewed in Cheli et al, 2010; Goding and Arnheiter, 2019).
所含基因
41 个基因