Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.4K
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...
2.4K
The Unfolded Protein Response01:37

The Unfolded Protein Response

4.4K
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...
4.4K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

10.7K
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...
10.7K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

3.0K
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,...
3.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Effects of Talker Sex Differences on Binaural Summation in Cochlear Implant Users and Normal Hearing Listeners.

Trends in hearing·2026
Same author

A Systematic Comparison of Multiple Models for Depth-Dependent Decay of Hydraulic Conductivity in Salt Lake Areas: A Case Study of Typical Boreholes in the Qaidam Basin.

Water environment research : a research publication of the Water Environment Federation·2026
Same author

Octanoic acid treatment alleviates cold-induced depression-like behaviors via targeting the AKR1B1-PGF2α pathway.

iScience·2026
Same author

Cellular mechanisms of osteoporosis: A comprehensive perspective on ferroptosis, cuproptosis and lipid metabolism abnormalities.

Biomaterials translational·2026
Same author

Light-based modulation of astrocytic calcium for regulation of organelle dynamics and morphogenesis.

The Journal of cell biology·2026
Same author

Binaural Processing Is Key to Tonal-Language Benefits and Right-Ear Advantage for Segregation of Competing Speech.

Journal of speech, language, and hearing research : JSLHR·2026
Same journal

The exquisite mechanics of a tsetse bite.

eLife·2026
Same journal

Distinct involvements of the subthalamic nucleus subpopulations in reward-biased decision-making in monkeys.

eLife·2026
Same journal

Pink1-mediated mitophagy in the endothelium releases proteins encoded by mitochondrial DNA and activates neutrophil responses during inflammation.

eLife·2026
Same journal

Restraint of melanoma progression by cells in the local skin environment.

eLife·2026
Same journal

Brawn before bite in endemic Asian eutherian mammals after the end-Cretaceous extinction.

eLife·2026
Same journal

Experimental evolution to thermal stress indicates climate resilience in a cosmopolitan arthropod.

eLife·2026
See all related articles

Related Experiment Video

Updated: May 30, 2025

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.8K

PEBP1 amplifies mitochondrial dysfunction-induced integrated stress response.

Ling Cheng1, Ian Meliala1, Yidi Kong1

  • 1Centre for Cellular Biology and Signalling, Zhejiang University-University of Edinburgh (ZJU-UoE) Institute, Haining, China.

Elife
|January 29, 2025
PubMed
Summary
This summary is machine-generated.

Phosphatidylethanolamine-binding protein 1 (PEBP1) amplifies mitochondrial stress responses by interacting with eukaryotic translation initiation factor 2α (eIF2α). This finding reveals PEBP1 as a potential therapeutic target for mitochondrial dysfunction diseases.

Keywords:
PEBP1cell biologyhumanintegrated stress responsemitochondrial dysfunction

More Related Videos

Author Spotlight: New Insights into PBMC Mitochondrial Responses Using Fluorespirometry
07:18

Author Spotlight: New Insights into PBMC Mitochondrial Responses Using Fluorespirometry

Published on: May 24, 2024

934
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

1.5K

Related Experiment Videos

Last Updated: May 30, 2025

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.8K
Author Spotlight: New Insights into PBMC Mitochondrial Responses Using Fluorespirometry
07:18

Author Spotlight: New Insights into PBMC Mitochondrial Responses Using Fluorespirometry

Published on: May 24, 2024

934
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

1.5K

Area of Science:

  • Mitochondrial biology
  • Cellular stress response
  • Molecular mechanisms of disease

Background:

  • Mitochondrial dysfunction is implicated in aging and various diseases.
  • The integrated stress response (ISR) is a key cellular adaptation to stress, including mitochondrial stress.
  • Understanding the molecular players in mitochondrial ISR is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of phosphatidylethanolamine-binding protein 1 (PEBP1) in the mitochondrial integrated stress response (ISR).
  • To elucidate the mechanism by which PEBP1 influences ISR activation and mitochondrial stress signaling.
  • To assess the therapeutic potential of PEBP1 in conditions related to mitochondrial dysfunction.

Main Methods:

  • Mass spectrometry-based cellular thermal shift assay (MS-CETSA) to identify proteins stabilized by mitochondrial ISR.
  • Gene silencing (depletion) and overexpression of PEBP1 to assess its functional impact on ISR.
  • Luminescence complementation assays to study protein-protein interactions in live cells.

Main Results:

  • PEBP1 is thermally stabilized by stresses inducing mitochondrial ISR, indicating its involvement.
  • PEBP1 depletion impairs mitochondrial ISR activation, evidenced by reduced eIF2α phosphorylation and downstream gene expression.
  • PEBP1 interacts with eIF2α, and this interaction is modulated by eIF2α phosphorylation, independent of the RAF/MEK/ERK pathway.
  • PEBP1 potentiates ISR activation mediated by HRI kinase.

Conclusions:

  • PEBP1 plays a significant role in amplifying mitochondrial stress signals, thereby enhancing cellular adaptation to mitochondrial dysfunction.
  • PEBP1's interaction with eIF2α is a key mechanism in its function within the mitochondrial ISR pathway.
  • PEBP1 represents a promising therapeutic target for treating diseases associated with mitochondrial dysfunction.