A novel import route for an N-anchor mitochondrial outer membrane protein aided by the TIM23 complex

Jiyao Song1, Yasushi Tamura2, Tohru Yoshihisa3

  • 1Department of Chemistry, Graduate School of Science Nagoya University, Chikusa-ku Nagoya, Japan.

EMBO Reports
|May 1, 2014
PubMed

Insights

Om45 anchors to the yeast mitochondrial outer membrane (OM) from the intermembrane space (IMS). This novel OM protein import pathway utilizes the TIM23 complex and membrane potential (ΔΨ).

Area of Science:

  • Mitochondrial biology
  • Protein import
  • Cellular membrane topology

Background:

  • The precise membrane topology of Om45 in the yeast mitochondrial outer membrane (OM) remains a subject of scientific discussion.
  • Understanding the mechanisms of outer membrane protein insertion is crucial for mitochondrial function.

Purpose of the Study:

  • To elucidate the membrane topology and import pathway of the Om45 protein in yeast mitochondria.
  • To identify the specific protein complexes and membrane potentials involved in Om45 translocation.

Main Methods:

  • Utilized yeast as a model organism.
  • Investigated protein import pathways using genetic and biochemical approaches.
  • Confirmed protein anchoring and localization within mitochondrial membranes.

Main Results:

  • Om45 is confirmed to be anchored to the OM from the intermembrane space (IMS) via its N-terminal hydrophobic segment.
  • Om45 import necessitates the presequence receptors Tom20 and Tom22, and the Tom40 import channel.
  • Uniquely, Om45 import requires the inner membrane TIM23 complex and the membrane potential (ΔΨ).

Conclusions:

  • Om45 is anchored to the mitochondrial outer membrane from the intermembrane space.
  • A novel protein import pathway involving the TIM23 complex facilitates Om45 translocation across the outer membrane.
  • This pathway highlights a previously unrecognized mechanism for outer membrane protein insertion in yeast mitochondria.

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...
3.5K
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...
4.4K
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,...
8.8K
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...
2.9K
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...
2.0K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
4.6K