Related Experiment Video
Updated: Jan 5, 2026
05:52
Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
2.9K
Molecular pathways of mitochondrial outer membrane protein degradation
Jing Zheng1,2,3, Lanlan Li2,3,4, Hui Jiang2,3,5
1Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing 100871, China.
Biochemical Society Transactions
|October 26, 2019
Summary
Six mitochondrial outer membrane protein degradation pathways maintain mitochondrial health. These pathways utilize AAA ATPases to clear misfolded proteins and ensure proper mitochondrial function and cell viability.
Area of Science:
- Mitochondrial biology
- Cellular quality control
- Protein homeostasis
Background:
- The mitochondrial outer membrane (MOM) is crucial for regulating mitochondrial functions.
- Recent research has elucidated MOM-associated proteostatic stresses and quality control mechanisms.
Purpose of the Study:
- To detail the six MOM-associated protein degradation (MAD) pathways.
- To explain how these pathways maintain mitochondrial proteostasis.
Main Methods:
- Focus on the roles of AAA ATPases: Cdc48, Msp1, and Yme1.
- Description of pathway surveillance from cytoplasmic and inter-membrane space (IMS) sides.
Main Results:
- These pathways degrade MOM proteins with misfolded domains.
- They remove mistargeted tail-anchored proteins.
- They clear precursor proteins from the TOM import complex.
Conclusions:
- The six MAD pathways collaboratively maintain mitochondrial proteostasis.
- These quality control mechanisms are essential for cell viability.
Related Concept Videos
01:12Porin Insertion in the Outer Mitochondrial Membrane
4.4K
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...
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...
4.4K
01:19Translocation of Proteins into the Mitochondria
11.8K
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,...
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,...
11.8K
01:39Mitochondrial Protein Sorting
5.5K
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...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
5.5K
01:21Structure of Porins
3.7K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.7K
01:39Mitochondrial Precursor Proteins
3.5K
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...
Most of the mitochondrial...
3.5K
01:32Export of Misfolded Proteins out of the ER
4.9K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.9K