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Updated: Jun 17, 2025

Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol
Zachary N Wilson1, Matt West2, Alyssa M English1
1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Abstract:
Preserving the health of the mitochondrial network is critical to cell viability and longevity. To do so, mitochondria employ several membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and compartments (MDCs) to selectively remove portions of the organelle. In contrast to well-characterized MDVs, the distinguishing features of MDC formation and composition remain unclear. Here, we used electron tomography to observe that MDCs form as large, multilamellar domains that generate concentric spherical compartments emerging from mitochondrial tubules at ER-mitochondria contact sites. Time-lapse fluorescence microscopy of MDC biogenesis revealed that mitochondrial membrane extensions repeatedly elongate, coalesce, and invaginate to form these compartments that encase multiple layers of membrane. As such, MDCs strongly sequester portions of the outer mitochondrial membrane, securing membrane cargo into a protected domain, while also enclosing cytosolic material within the MDC lumen. Collectively, our results provide a model for MDC formation and describe key features that distinguish MDCs from other previously identified mitochondrial structures and cargo-sorting domains.
Insights
Mitochondria form unique compartments called mitochondrial-derived compartments (MDCs) to remove damaged parts. This study reveals how MDCs form and their distinct structure for cellular quality control.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Organelle Dynamics
Background:
- Mitochondrial health is crucial for cell viability and longevity.
- Mitochondria utilize mechanisms like mitochondrial-derived vesicles (MDVs) and compartments (MDCs) for organelle quality control.
- The formation and composition of MDCs are not well understood compared to MDVs.
Purpose of the Study:
- To elucidate the formation process and structural characteristics of mitochondrial-derived compartments (MDCs).
- To differentiate MDCs from other known mitochondrial structures and cargo-sorting mechanisms.
Main Methods:
- Electron tomography was employed to visualize MDC formation.
- Time-lapse fluorescence microscopy was used to observe MDC biogenesis in real-time.
- Analysis focused on mitochondrial tubules at ER-mitochondria contact sites.
Main Results:
- Mitochondrial-derived compartments (MDCs) originate as large, multilamellar domains at ER-mitochondria contact sites.
- MDC formation involves repeated elongation, coalescence, and invagination of mitochondrial membrane extensions.
- MDCs sequester outer mitochondrial membrane portions and enclose cytosolic material within a multilamellar structure.
Conclusions:
- A novel model for mitochondrial-derived compartment (MDC) formation is proposed.
- Key structural features distinguish MDCs from other mitochondrial vesicles and cargo-sorting domains.
- MDCs play a significant role in selective removal of mitochondrial components and cellular quality control.
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