期刊
CELL
卷 171, 期 2, 页码 331-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2017.08.041
关键词
-
资金
- NIH/NIDDK Center [5P30DK063608]
- Office of the NIH [S10OD020056]
- American Heart Association [11PRE7450075, 15POST25620024]
- KAKENHI from the Japanese Society for the Promotion of Science [17K09885]
- NIH [T32 HL007343-28, R37 NS036942, R01 HL093324, R01 HL075662, HL127464, HL132412]
- Grants-in-Aid for Scientific Research [17K09885] Funding Source: KAKEN
Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. We showhere that uptake of multiple ACs by macrophages requires dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, which is triggered by AC uptake. When mitochondrial fission is disabled, AC-induced increase in cytosolic calcium is blunted owing to mitochondrial calcium sequestration, and calcium-dependent phagosome formation around secondarily encountered ACs is impaired. These defects can be corrected by silencing the mitochondrial calcium uniporter (MCU). Mice lacking myeloid Drp1 showed defective efferocytosis and its pathologic consequences in the thymus after dexamethasone treatment and in advanced atherosclerotic lesions in fat-fed Ldlr(-/-) mice. Thus, mitochondrial fission in response to AC uptake is a critical process that enables macrophages to clear multiple ACs and to avoid the pathologic consequences of defective efferocytosis in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据