Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales Sydney, Kensington, NSW 2052, Australia.
Palaeontology, Geobiology and Earth Archives Research Centre, University of New South Wales Sydney, Kensington, NSW 2052, Australia.
Int J Mol Sci. 2020 Sep 3;21(17):6422. doi: 10.3390/ijms21176422.
The transitioning of cells during the systemic demise of an organism is poorly understood. Here, we present evidence that organismal death is accompanied by a common and sequential molecular flood of stress-induced events that propagate the senescence phenotype, and this phenotype is preserved in the proteome after death. We demonstrate activation of "death" pathways involvement in diseases of ageing, with biochemical mechanisms mapping onto neurological damage, embryonic development, the inflammatory response, cardiac disease and ultimately cancer with increased significance. There is sufficient bioavailability of the building blocks required to support the continued translation, energy, and functional catalytic activity of proteins. Significant abundance changes occur in 1258 proteins across 1 to 720 h post-mortem of the 12-week-old mouse mandible. Protein abundance increases concord with enzyme activity, while mitochondrial dysfunction is evident with metabolic reprogramming. This study reveals differences in protein abundances which are akin to states of stress-induced premature senescence (SIPS). The control of these pathways is significant for a large number of biological scenarios. Understanding how these pathways function during the process of cellular death holds promise in generating novel solutions capable of overcoming disease complications, maintaining organ transplant viability and could influence the findings of proteomics through "deep-time" of individuals with no historically recorded cause of death.
细胞在生物体系统性死亡过程中的转变机制还不太清楚。在这里，我们提供的证据表明，生物体死亡伴随着一系列共同的、顺序发生的应激诱导事件，这些事件会引发衰老表型，而这种表型在死亡后仍然存在于蛋白质组中。我们发现参与衰老疾病的“死亡”途径被激活，生化机制映射到神经损伤、胚胎发育、炎症反应、心脏病，最终是癌症，其重要性增加。有足够的生物可利用性来支持蛋白质的持续翻译、能量和功能催化活性所需的构建块。在 12 周大的老鼠下颚死后 1 到 720 小时，有 1258 种蛋白质的丰度发生了显著变化。蛋白质丰度的增加与酶活性一致，而线粒体功能障碍则伴随着代谢重编程。这项研究揭示了蛋白质丰度的差异类似于应激诱导的过早衰老（SIPS）状态。这些途径的控制对许多生物学场景都很重要。了解这些途径在细胞死亡过程中的功能有望产生新的解决方案，能够克服疾病并发症，维持器官移植的活力，并可能通过“深度时间”影响没有历史记录的死因的个体的蛋白质组学发现。
