INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division. Academic Article uri icon

Overview

abstract

  • Mitochondrial division requires division of both the inner and outer mitochondrial membranes (IMM and OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM division by recruitment of the dynamin Drp1, but effects on IMM division are not well characterized. We previously showed that actin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 recruitment in mammalian cells. Here, we show that INF2-mediated actin polymerization stimulates a second mitochondrial response independent of Drp1: a rise in mitochondrial matrix calcium through the mitochondrial calcium uniporter. ER stores supply the increased mitochondrial calcium, and the role of actin is to increase ER-mitochondria contact. Myosin IIA is also required for this mitochondrial calcium increase. Elevated mitochondrial calcium in turn activates IMM constriction in a Drp1-independent manner. IMM constriction requires electron transport chain activity. IMM division precedes OMM division. These results demonstrate that actin polymerization independently stimulates the dynamics of both membranes during mitochondrial division: IMM through increased matrix calcium, and OMM through Drp1 recruitment.

publication date

  • November 15, 2017

Research

keywords

  • Actins
  • Cell Division
  • Endoplasmic Reticulum
  • Microfilament Proteins
  • Mitochondria
  • Mitochondrial Membranes

Identity

PubMed Central ID

  • PMC5748994

Scopus Document Identifier

  • 85039838794

Digital Object Identifier (DOI)

  • 10.1126/science.1219855

PubMed ID

  • 29142021

Additional Document Info

volume

  • 217

issue

  • 1