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Updated: Jul 7, 2026

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
The outer membrane form of the mitochondrial protein Mcr1 follows a TOM-independent membrane insertion pathway
Birthe Meineke1, Gertraud Engl, Christian Kemper
1Interfaculty Institute for Biochemistry, Hoppe-Seyler-Strasse 4, University of Tübingen, 72076 Tübingen, Germany.
Abstract:
The yeast gene MCR1 encodes two isoforms of the mitochondrial NADH-cytochrome b5 reductase. One form is embedded in the outer membrane whereas the other is located in the intermembrane space (IMS). In the present work we investigated the biogenesis of the outer membrane form. We demonstrate that while the IMS form crosses the outer membrane via the translocase of the outer mitochondrial membrane (TOM) complex, the other form is integrated into the outer membrane by a process that does not require any of the known import components at the outer membrane. Thus, the import pathways of the two forms diverge in a stage before the encounter with the TOM complex and their mechanism of biogenesis represents a unique example how to achieve dual localization within one organelle.
Insights
The yeast MCR1 gene produces two mitochondrial NADH-cytochrome b5 reductase forms. Their distinct biogenesis pathways diverge before the TOM complex, showcasing a unique dual organelle localization mechanism.
Area of Science:
- Mitochondrial biogenesis
- Protein targeting
- Yeast genetics
Background:
- The yeast MCR1 gene encodes two isoforms of mitochondrial NADH-cytochrome b5 reductase.
- One isoform resides in the outer mitochondrial membrane, while the other is located in the intermembrane space (IMS).
Purpose of the Study:
- To investigate the biogenesis pathway of the outer mitochondrial membrane-bound form of NADH-cytochrome b5 reductase.
- To elucidate the distinct import mechanisms of the two MCR1 isoforms.
Main Methods:
- Utilized yeast genetics and protein localization studies.
- Investigated protein import pathways across the mitochondrial outer membrane.
Main Results:
- The intermembrane space (IMS) form of NADH-cytochrome b5 reductase utilizes the translocase of the outer mitochondrial membrane (TOM) complex for import.
- The outer membrane form is integrated via a novel pathway independent of known outer membrane import components.
- The divergence in import pathways occurs prior to interaction with the TOM complex.
Conclusions:
- The two MCR1 isoforms employ distinct biogenesis routes, highlighting a unique mechanism for achieving dual localization within a single organelle.
- This study reveals a novel mitochondrial protein targeting pathway independent of the canonical TOM complex.
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