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Updated: Jul 18, 2025

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

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Nix interacts with WIPI2 to induce mitophagy

Eric N Bunker1, François Le Guerroué1, Chunxin Wang1

  • 1Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

The EMBO Journal
|August 25, 2023
PubMed

Insights

Nix protein initiates mitophagy by interacting with WIPI2 via its minimal essential region (MER) and with ATG8 proteins via its LC3-interacting (LIR) motif. Both interactions are crucial for efficient mitophagy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Nix is an outer mitochondrial protein that triggers mitophagy, a selective form of autophagy.
  • Nix possesses an LC3-interacting (LIR) motif for ATG8 binding and a minimal essential region (MER) with an undefined role in mitophagy.
  • The precise mechanism by which Nix induces mitophagy, particularly the function of its MER, remains largely unknown.

Purpose of the Study:

  • To elucidate the mechanism of Nix-mediated mitophagy, focusing on the roles of the LIR motif and MER.
  • To investigate how Nix interacts with other autophagy-related proteins during mitophagy induction.
  • To understand the upstream events in Nix-induced mitophagy independent of canonical initiation complexes.

Main Methods:

  • Utilized chemically induced dimerization (CID) to dissect the functions of Nix's LIR motif and MER.
  • Investigated protein-protein interactions between Nix, WIPI2, and ATG8 proteins.
  • Analyzed the subcellular localization of WIPI2 in response to Nix and its domains.

Main Results:

  • Both the LIR motif and MER of Nix are essential for robust mitophagy.
  • The Nix MER directly interacts with and recruits the autophagy effector WIPI2 to mitochondria.
  • The Nix LIR motif is necessary for converting homogeneous WIPI2 distribution into puncta, even without ATG8 proteins.

Conclusions:

  • Nix-induced mitophagy involves a novel mechanism where the MER recruits WIPI2, and the LIR motif further organizes WIPI2.
  • This study reveals the elusive function of the Nix MER in initiating mitophagy.
  • Nix provides an example of autophagy induction acting downstream of canonical initiation complexes, highlighting alternative pathways in autophagy regulation.
Keywords:
AutophagyBNIP3FIP200LIRp62

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