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Published on: April 18, 2016
Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation
Mariusz Karbowski1, Richard J Youle
1Center for Biomedical Engineering and Technology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. mkarbowski@umaryland.edu
Current Opinion in Cell Biology
|June 28, 2011
Summary
Mitochondrial outer membrane proteins are ubiquitinated and degraded by the proteasome, involving the AAA ATPase cdc48/p97/VCP. This pathway regulates apoptosis and mitophagy, with its full scope still under investigation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitochondrial outer membrane proteins are subject to ubiquitination and proteasomal degradation.
- This process utilizes components of the ER-associated degradation (ERAD) pathway, including the AAA ATPase cdc48/p97/VCP.
- cdc48/p97/VCP is implicated in extracting integral membrane proteins from lipid bilayers for proteasomal processing.
Purpose of the Study:
- To explore the mechanisms and physiological relevance of outer mitochondrial membrane (OMM) protein turnover.
- To understand the role of ubiquitination and proteasomal degradation in regulating mitochondrial function and cellular processes.
Main Methods:
- Investigating protein ubiquitination on the OMM.
- Analyzing the involvement of the ERAD pathway component cdc48/p97/VCP in OMM protein degradation.
- Examining specific examples like Mcl1 degradation in apoptosis and Mitofusin degradation in mitophagy.
Main Results:
- The proteasomal degradation of OMM proteins is a significant cellular process.
- The AAA ATPase cdc48/p97/VCP plays a role in OMM protein extraction and delivery to the proteasome.
- Specific OMM proteins like Mcl1 and Mitofusins are regulated by this degradation pathway, impacting apoptosis, mitochondrial fusion, and mitophagy.
Conclusions:
- Ubiquitin-proteasome system mediated degradation is crucial for OMM protein turnover.
- This pathway is linked to key cellular events including apoptosis, mitochondrial dynamics, and mitophagy.
- Further research is needed to fully elucidate the range of OMM substrates and the physiological importance of their regulated degradation.
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