Related Experiment Video
Updated: Apr 19, 2026
10:12
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
2.9K
The mitochondrial unfolded protein response—synchronizing genomes.
Virginija Jovaisaite1, Johan Auwerx1
1Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Current Opinion in Cell Biology
|December 30, 2014
Summary
The mitochondrial unfolded protein response (UPR(mt)) is a crucial cellular pathway that maintains mitochondrial proteome quality. This review explores UPR(mt) signaling, its role in cellular repair, and implications for health and lifespan.
Area of Science:
- Mitochondrial Biology
- Cellular Stress Response
- Molecular Signaling
Background:
- Mitochondria rely on chaperones and proteases for proteome maintenance.
- Mitochondrial stress triggers a nuclear response to repair damage.
- The mitochondrial unfolded protein response (UPR(mt)) links mitochondrial and nuclear genomes.
Purpose of the Study:
- To review recent advances in the UPR(mt) field.
- To discuss UPR(mt) induction, signaling, and communication pathways.
- To explore the implications of UPR(mt) in health and lifespan.
Main Methods:
- Literature review of UPR(mt) research.
- Analysis of signaling pathways involved in UPR(mt).
- Discussion of regulatory network interactions.
Main Results:
- UPR(mt) is activated by various mitochondrial stresses.
- This response involves communication between mitochondria and the nucleus.
- UPR(mt) synchronizes genomic activities for proteome quality control.
Conclusions:
- UPR(mt) is essential for maintaining mitochondrial proteome integrity.
- Understanding UPR(mt) offers insights into cellular adaptation and disease.
- UPR(mt) pathways hold potential therapeutic targets for age-related diseases.
Related Concept Videos
01:37The Unfolded Protein Response
7.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
7.1K
01:31Regulation of the Unfolded Protein Response
3.3K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.3K
01:32Export of Misfolded Proteins out of the ER
5.7K
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...
5.7K
01:39Mitochondrial Precursor Proteins
3.9K
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...
3.9K
01:39Mitochondrial Protein Sorting
6.0K
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...
6.0K
01:19Translocation of Proteins into the Mitochondria
13.8K
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,...
13.8K