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INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction,

Rajarshi Chakrabarti1, Wei-Ke Ji1, Radu V Stan1

  • 1Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH.

The Journal of Cell Biology
|November 17, 2017
PubMed

Insights

Actin polymerization drives mitochondrial division by independently stimulating both membranes. It increases matrix calcium for inner membrane constriction and recruits Drp1 for outer membrane division.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Membrane Biology

Background:

  • Mitochondrial division necessitates coordinated division of the inner and outer mitochondrial membranes (IMM and OMM).
  • Endoplasmic reticulum (ER) interaction aids OMM division via Drp1, but IMM division mechanisms remain unclear.
  • Previous work linked actin polymerization (via INF2) to Drp1 recruitment for OMM division.

Purpose of the Study:

  • To investigate the role of actin polymerization in IMM division.
  • To elucidate the mechanisms by which ER-mitochondria contact influences mitochondrial division.
  • To determine if actin affects mitochondrial division independently of Drp1.

Main Methods:

  • Utilized mammalian cell cultures.
  • Investigated the effects of actin polymerization (induced by INF2) on mitochondrial calcium levels.
  • Assessed the role of ER calcium stores, mitochondrial calcium uniporter, and Myosin IIA.
  • Examined the requirement of electron transport chain activity for IMM constriction.
  • Observed the temporal relationship between IMM and OMM division.

Main Results:

  • INF2-mediated actin polymerization triggers a Drp1-independent rise in mitochondrial matrix calcium.
  • This calcium increase is supplied by ER stores and facilitated by enhanced ER-mitochondria contact.
  • Myosin IIA is essential for the actin-stimulated mitochondrial calcium increase.
  • Elevated mitochondrial calcium activates IMM constriction, dependent on electron transport chain activity.
  • IMM division was observed to precede OMM division.

Conclusions:

  • Actin polymerization independently regulates both mitochondrial membranes during division.
  • It promotes IMM constriction via a Drp1-independent pathway involving calcium signaling.
  • It facilitates OMM division through Drp1 recruitment, as previously shown.
  • This study reveals a dual role for actin in orchestrating mitochondrial membrane dynamics.

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