Video Experimental Relacionado
Updated: Oct 18, 2025
14:29
Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells
Published on: December 25, 2021
4.3K
La respuesta integrada al estrés combina la traducción de proteínas mitocondriales con el control del estrés
Guangyu Zhang1, Xiaoding Wang1, Chao Li1
1Division of Cardiology (G.Z., X.W., C.L., Q.L., X.L., T.G.G., Z.V.W.), Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Circulation
|September 29, 2021
Resumen
La respuesta integrada al estrés (ISR) protege el corazón durante la lesión de reperfusión después del infarto de miocardio. La activación de la ISR reduce el daño cardíaco al suprimir la síntesis de proteínas mitocondriales y el estrés oxidativo.
Área de la Ciencia:
- Cardiología
- Biología molecular
- Respuesta Celular al Estrés
Sus antecedentes:
- El infarto de miocardio es una de las principales causas de muerte a nivel mundial.
- La reperfusión de la arteria coronaria, aunque salva vidas, puede causar más daño cardíaco (lesión por reperfusión).
- La respuesta integrada al estrés (ISR) es un mecanismo celular que responde a las perturbaciones.
Objetivo del estudio:
- Investigar el papel de la ISR en la lesión de isquemia/reperfusión (I/R) del miocardio.
- Explorar el potencial terapéutico de la manipulación de la ISR para el tratamiento del infarto de miocardio.
Principales métodos:
- Se utilizaron modelos in vivo de ganancia y pérdida de función específicos del corazón.
- I/R miocárdico inducido por ligadura y reperfusión de la arteria coronaria.
- Se evaluó la función cardíaca mediante ecocardiografía y se analizaron los mecanismos moleculares en cultivos celulares y tejidos.
- Se utilizó la espectrometría de masas para identificar los objetivos de las proteínas ISR y se probaron las intervenciones farmacológicas.
Principales resultados:
- El eje PERK (cinasa residente en el retículo endoplasmático similar a PKR) /eIF2α (subunidad α del factor de iniciación eucariota 2) de la ISR fue inducido significativamente por I/R.
- La activación de la señalización cardíaca PERK/ eIF2α confirió cardioprotección contra la lesión por reperfusión.
- PERK se dirige a NDUFAF2 (NADH: ubiquinona oxidoreductasa complejo factor de ensamblaje 2), un factor de ensamblaje del complejo mitocondrial I, suprimiendo su expresión.
- La activación de ISR redujo las especies de oxígeno reactivo mitocondrial y mejoró la supervivencia de las células cardíacas.
Conclusiones:
- La ISR mejora la supervivencia de las células cardíacas y mitiga el daño por reperfusión.
- Esta protección se consigue suprimiendo selectivamente la síntesis de proteínas mitocondriales y reduciendo el estrés oxidativo.
- La activación farmacológica de la ISR muestra relevancia clínica para el tratamiento del infarto de miocardio.
Videos de Conceptos Relacionados
01:19Translocation of Proteins into the Mitochondria
8.4K
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,...
8.4K
01:31Regulation of the Unfolded Protein Response
2.7K
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...
2.7K
01:45Mitochondrial Membranes
13.1K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
13.1K
01:46Electron Transport Chain: Complex I and II
15.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
15.3K
01:39Mitochondrial Protein Sorting
4.7K
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...
4.7K
01:37The Unfolded Protein Response
5.4K
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...
5.4K