Related Experiment Video

Updated: Jun 13, 2026

Rapid Isolation of the Mitoribosome from HEK Cells
09:33

Rapid Isolation of the Mitoribosome from HEK Cells

Published on: October 4, 2018

MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria

Yehudit Zaltsman1, Liat Shachnai1, Natalie Yivgi-Ohana1

  • 1Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.

Nature Cell Biology
|May 4, 2010
PubMed

Insights

MTCH2/MIMP is a novel protein that helps recruit truncated BID (tBID) to mitochondria, a key step in liver apoptosis. Its absence impairs tBID recruitment, mitochondrial outer membrane permeabilization, and liver cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The BH3-only BID protein initiates the death-receptor pathway in liver cells by triggering mitochondrial outer membrane permeabilization (MOMP).
  • Understanding the regulation of tBID (truncated BID) recruitment to mitochondria is crucial for comprehending liver apoptosis.

Purpose of the Study:

  • To identify and characterize novel proteins involved in the recruitment of tBID to the outer mitochondrial membrane.
  • To elucidate the role of MTCH2/MIMP in liver apoptosis and its interaction with tBID.

Main Methods:

  • Utilized knockout models (embryonic stem cells, mouse embryonic fibroblasts, and conditional liver knockout mice) to study MTCH2/MIMP function.
  • Investigated the effects of MTCH2/MIMP deletion on tBID recruitment, Bax/Bak activation, MOMP, and apoptosis induction.
  • Performed in vivo and in vitro experiments to assess liver apoptosis sensitivity and tBID localization.

Main Results:

  • Identified MTCH2/MIMP as a novel outer mitochondrial membrane protein that facilitates tBID recruitment.
  • MTCH2/MIMP knockout hindered tBID recruitment, Bax/Bak activation, MOMP, and apoptosis in various cell types.
  • Conditional liver knockout of MTCH2/MIMP reduced sensitivity to Fas-induced apoptosis and impaired tBID recruitment to liver mitochondria.

Conclusions:

  • MTCH2/MIMP plays a critical role in liver apoptosis by regulating tBID recruitment to mitochondria.
  • MTCH2/MIMP's function is specific to the tBID-mediated apoptotic pathway and does not affect other pro-apoptotic Bcl-2 family members.
  • MTCH2/MIMP is essential for initiating MOMP and subsequent apoptosis in liver cells via the death-receptor pathway.

More Related Videos

Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria11:53

Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria

Published on: September 18, 2014

An Improved Method to Isolate Mitochondrial Contact Sites07:55

An Improved Method to Isolate Mitochondrial Contact Sites

Published on: June 16, 2023

Related Concept Videos

Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...