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Drp1 Tubulates the ER in a GTPase-Independent Manner

Yoshihiro Adachi1, Takashi Kato1, Tatsuya Yamada1

  • 1Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Molecular Cell
|November 5, 2020
PubMed

Insights

Mitochondrial division relies on dynamin-related protein (Drp1), which shapes endoplasmic reticulum (ER) tubules. This ER shaping by Drp1, independent of GTP hydrolysis, promotes mitochondrial division by enhancing ER-mitochondria interactions.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Endoplasmic Reticulum Structure

Background:

  • Mitochondria are dynamic organelles essential for cellular function, undergoing constant growth, division, and fusion.
  • Mitochondrial division is a critical process for human health, involving the protein dynamin-related protein (Drp1).
  • Drp1 mediates mitochondrial division at endoplasmic reticulum (ER)-mitochondria contact sites, where ER tubules interact with mitochondria.

Purpose of the Study:

  • To investigate the direct role of Drp1 in shaping peripheral ER tubules.
  • To determine if Drp1's ER-shaping activity is linked to its GTPase function.
  • To elucidate the mechanism by which Drp1 influences ER-mitochondria interactions and mitochondrial division.

Main Methods:

  • Studied Drp1's effect on ER tubule morphology in human and mouse cells.
  • Investigated the role of a specific Drp1 peptide (D-octadecapeptide) in ER tubulation.
  • Utilized in vitro liposome tubulation assays and cellular experiments to assess ER tubule formation.

Main Results:

  • Drp1 directly shapes peripheral ER tubules in a GTP hydrolysis-independent manner.
  • A conserved 18-amino acid peptide (D-octadecapeptide) within Drp1 is responsible for ER tubulation.
  • Synthetic D-octadecapeptide effectively tubulates both liposomes in vitro and the ER in cells.
  • Drp1-induced ER tubules enhance ER-mitochondria interactions, promoting mitochondrial division.

Conclusions:

  • Drp1 possesses a dual function in mitochondrial division: acting as a mechano-GTPase and directly shaping ER tubules.
  • The ER-shaping activity of Drp1, mediated by the D-octadecapeptide, is crucial for facilitating mitochondrial division.
  • Drp1's ability to promote ER tubulation represents a novel mechanism for regulating mitochondrial dynamics.
Keywords:
Drp1mitochondriamitochondrial divisionorganelle contact sitesphosphaditic acidthe endoplasmic reticulum

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