Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
Arch Biochem Biophys. 2020 Dec 15;696:108668. doi: 10.1016/j.abb.2020.108668. Epub 2020 Nov 11.
Mitochondria are multifunctional organelles that regulate diverse cellular processes. Mitochondrial stress, including stress generated by electron transport chain defects and impaired mitochondrial proteostasis, is intimately involved in various diseases and pathological conditions. Sepsis is a life-threatening condition that occurs when an imbalanced host response to infection leads to organ dysfunction. Metabolic disturbances and impaired immune responses are implicated in the pathogenesis and development of sepsis. Given that mitochondria play central roles in cellular metabolism, mitochondrial stress is predicted to be involved in the pathological mechanism of sepsis. Under mitochondrial stress, cells activate stress response systems to maintain homeostasis. This mitochondrial stress response transcriptionally activates genes involved in cell survival and death. Mitochondrial stress also induces the release of distinctive secretory proteins from cells. Recently, we showed that growth differentiation factor 15 (GDF15) is a major secretory protein induced by mitochondrial dysfunction. In this article, we provide a brief overview of mitochondrial stress response and GDF15, and discuss the potential role of GDF15 in the pathophysiology of sepsis.
线粒体是具有多种功能的细胞器，调节着各种细胞过程。线粒体应激，包括电子传递链缺陷和线粒体蛋白稳态受损引起的应激，与各种疾病和病理状况密切相关。败血症是一种危及生命的病症，当宿主对感染的失衡反应导致器官功能障碍时就会发生。代谢紊乱和受损的免疫反应与败血症的发病机制和发展有关。鉴于线粒体在细胞代谢中起着核心作用，线粒体应激预计与败血症的病理机制有关。在线粒体应激下，细胞激活应激反应系统以维持体内平衡。这种线粒体应激反应转录激活与细胞存活和死亡相关的基因。线粒体应激还诱导细胞释放独特的分泌蛋白。最近，我们发现生长分化因子 15（GDF15）是一种由线粒体功能障碍诱导的主要分泌蛋白。在本文中，我们简要概述了线粒体应激反应和 GDF15，并讨论了 GDF15 在败血症病理生理学中的潜在作用。
