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Updated: Jun 17, 2025

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
Mitochondrial-derived compartments remove surplus proteins from the outer mitochondrial membrane
Zachary N Wilson1, Sai Sangeetha Balasubramaniam1, Sara Wong1
1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Abstract:
The outer mitochondrial membrane (OMM) creates a boundary that imports most of the mitochondrial proteome while removing extraneous or damaged proteins. How the OMM senses aberrant proteins and remodels to maintain OMM integrity remains unresolved. Previously, we identified a mitochondrial remodeling mechanism called the mitochondrial-derived compartment (MDC) that removes a subset of the mitochondrial proteome. Here, we show that MDCs specifically sequester proteins localized only at the OMM, providing an explanation for how select mitochondrial proteins are incorporated into MDCs. Remarkably, selective sorting into MDCs also occurs within the OMM, as subunits of the translocase of the outer membrane (TOM) complex are excluded from MDCs unless assembly of the TOM complex is impaired. Considering that overloading the OMM with mitochondrial membrane proteins or mistargeted tail-anchored membrane proteins induces MDCs to form and sequester these proteins, we propose that one functional role of MDCs is to create an OMM-enriched trap that segregates and sequesters excess proteins from the mitochondrial surface.
Insights
Mitochondrial-derived compartments (MDCs) sequester excess outer mitochondrial membrane proteins. This mechanism helps maintain mitochondrial integrity by trapping aberrant proteins on the mitochondrial surface.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Protein Homeostasis
Background:
- The outer mitochondrial membrane (OMM) regulates protein import and removal of damaged proteins.
- The mechanism by which the OMM senses and removes aberrant proteins is not fully understood.
- Mitochondrial-derived compartments (MDCs) were previously identified as a mechanism for removing mitochondrial proteins.
Purpose of the Study:
- To investigate how the OMM senses aberrant proteins and maintains its integrity.
- To elucidate the role of MDCs in managing the OMM proteome.
- To understand the selective sorting of proteins into MDCs.
Main Methods:
- Investigated protein localization and sequestration within MDCs.
- Analyzed the role of the translocase of the outer membrane (TOM) complex assembly in MDC formation.
- Studied the effects of excess mitochondrial membrane proteins and mistargeted proteins on MDC formation.
Main Results:
- MDCs specifically sequester proteins localized to the OMM.
- Subunits of the TOM complex are excluded from MDCs unless TOM assembly is impaired.
- Overloading the OMM with proteins induces MDC formation and sequestration.
Conclusions:
- MDCs selectively trap OMM-localized proteins.
- MDCs play a role in maintaining OMM integrity by sequestering excess or aberrant proteins.
- MDCs function as an OMM-enriched trap to segregate proteins from the mitochondrial surface.
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