Varga M, Sass M, Papp D, Takács-Vellai K, Kobolak J, Dinnyés A, Klionsky D J, Vellai T
Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
Cell Death Differ. 2014 Apr;21(4):547-56. doi: 10.1038/cdd.2013.175. Epub 2013 Dec 6.
Regeneration is the ability of multicellular organisms to replace damaged tissues and regrow lost body parts. This process relies on cell fate transformation that involves changes in gene expression as well as in the composition of the cytoplasmic compartment, and exhibits a characteristic age-related decline. Here, we present evidence that genetic and pharmacological inhibition of autophagy - a lysosome-mediated self-degradation process of eukaryotic cells, which has been implicated in extensive cellular remodelling and aging - impairs the regeneration of amputated caudal fins in the zebrafish (Danio rerio). Thus, autophagy is required for injury-induced tissue renewal. We further show that upregulation of autophagy in the regeneration zone occurs downstream of mitogen-activated protein kinase/extracellular signal-regulated kinase signalling to protect cells from undergoing apoptosis and enable cytosolic restructuring underlying terminal cell fate determination. This novel cellular function of the autophagic process in regeneration implies that the role of cellular self-digestion in differentiation and tissue patterning is more fundamental than previously thought.
再生是多细胞生物替换受损组织和重新生长缺失身体部位的能力。这个过程依赖于细胞命运转变，这涉及基因表达以及细胞质区室组成的变化，并且呈现出与年龄相关的特征性衰退。在这里，我们提供证据表明，自噬的遗传和药理学抑制——真核细胞的一种溶酶体介导的自我降解过程，其与广泛的细胞重塑和衰老有关——会损害斑马鱼（Danio rerio）截断尾鳍的再生。因此，自噬是损伤诱导的组织更新所必需的。我们进一步表明，再生区自噬的上调发生在丝裂原活化蛋白激酶/细胞外信号调节激酶信号传导的下游，以保护细胞免于凋亡，并使终末细胞命运决定基础的胞质重组成为可能。自噬过程在再生中的这种新的细胞功能意味着细胞自我消化在分化和组织模式形成中的作用比以前认为的更为根本。
