Mitochondrial Fission Promotes the Continued Clearance of Apoptotic Cells by Macrophages. Academic Article uri icon

Overview

abstract

  • 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 show here 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.

publication date

  • September 21, 2017

Research

keywords

  • Macrophages
  • Mitochondrial Dynamics

Identity

PubMed Central ID

  • PMC5679712

Scopus Document Identifier

  • 85029682530

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2017.08.041

PubMed ID

  • 28942921

Additional Document Info

volume

  • 171

issue

  • 2