Endoplasmic reticulum (ER)-mitochondria contact sites are crucial to allow Ca flux between them and a plethora of proteins participate in tethering both organelles together. Inositol 1,4,5-trisphosphate receptors (IPRs) play a pivotal role at such contact sites, participating in both ER-mitochondria tethering and as Ca-transport system that delivers Ca from the ER towards mitochondria. At the ER-mitochondria contact sites, the IPRs function as a multi-protein complex linked to the voltage-dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane, via the chaperone glucose-regulated protein 75 (GRP75). This IPR-GRP75-VDAC1 complex supports the efficient transfer of Ca from the ER into the mitochondrial intermembrane space, from which the Ca ions can reach the mitochondrial matrix through the mitochondrial calcium uniporter. Under physiological conditions, basal Ca oscillations deliver Ca to the mitochondrial matrix, thereby stimulating mitochondrial oxidative metabolism. However, when mitochondrial Ca overload occurs, the increase in [Ca] will induce the opening of the mitochondrial permeability transition pore, thereby provoking cell death. The IPR-GRP75-VDAC1 complex forms a hub for several other proteins that stabilize the complex and/or regulate the complex's ability to channel Ca into the mitochondria. These proteins and their mechanisms of action are discussed in the present review with special attention for their role in pathological conditions and potential implication for therapeutic strategies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ceca.2023.102743 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Spontaneous Complexation-Exfoliation Strategy for a Flexible Anode Towards Superior Durable and Ultrafast Lithium-Ion Batteries.
Molecules
December 2024
College of Mechanical and Electronic Engineering, Tarim University, Alar 843300, China.
Article Synopsis
- Transition metal oxides, like MnO, show great promise as anodes for flexible electrodes but face challenges such as low conductivity and poor cycling performance.
- A new method called "spontaneous complexation and exfoliation" creates flexible thin-film electrodes using MnO nanocrystals and reduced graphene oxide (rGO), improving their mechanical flexibility and lithium-ion storage capacity.
- The resulting flexible anodes deliver around 1220 mAh/g over 1000 cycles with high-rate capacity, while maintaining performance even under bending, highlighting their potential for advanced energy storage solutions.
Sex-dependent adaptations in heart mitochondria from transgenic mice overexpressing cytochrome b reductase-3.
Mitochondrion
January 2025
Departamento de Biología Celular Fisiología e Inmunología Universidad de Córdoba Campus de Excelencia Internacional Agroalimentario ceiA3 Córdoba Spain. Electronic address:
Cytochrome b reductase 3 (CYB5R3) overexpression upregulates mitochondrial biogenesis, function, and abundance in skeletal muscle and kidneys, and mimics some of the salutary effects of calorie restriction, with the most striking effects being observed in females. We aimed to investigate the mitochondrial adaptations prompted by CYB5R3 overexpression in the heart, an organ surprisingly overlooked in studies focused on this long-lived transgenic model despite the critical role played by CYB5R3 in supporting cardiomyocytes mitochondrial respiration. Given that CYB5R3 effects have been found to be sex-dependent, we focused our research on both males and females.
View Article and Find Full Text PDFKnowing is Half the Battle: The Factors Leading to Efficient Recruitment of Representative Samples in Schizophrenia Research.
Pharmaceut Med
January 2025
New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032, USA.
Background And Objectives: Drug development in schizophrenia is limited by the differential scaling of the active treatment and placebo arms of a study, such that, as the number of sites increases, the magnitude of placebo response disproportionately increases. The objective of this article was to identify factors conducive to efficient recruitment as a step towards trial designs allowing recruitment of more participants per site, leading to reduced variability, and potentially a smaller placebo effect.
Patients And Methods: Using the information of 554 individuals, we calculated the percentage of individuals who were screened, consented, and retained in our research, along with rationale for nonconsent.
A test of the Grant-Stebbins pollinator-shift model of floral evolution.
New Phytol
January 2025
Department of Botany, Rhodes University, Makhanda, 6140, South Africa.
Pollinators are thought to play a key role in driving incipient speciation within the angiosperms. However, the mechanisms underlying floral divergence in plants with generalist pollination systems, remains understudied. Brunsvigia gregaria displays significant geographical variation in floral traits and are visited by diverse pollinator communities.
View Article and Find Full Text PDFEfficient activation of persulfate by copper-coated nano zero-valent iron for degradation of nitrogenous disinfection by-products: The key role of Cu.
J Colloid Interface Sci
January 2025
College of Ecological Environment and Urban Construction, Fujian University of Technology, Fuzhou, Fujian 350118, China. Electronic address:
The essential shortcoming of rapid passivation deactivation limits the efficient application of nano zero-valent iron (nZVI) in eliminating disinfection byproducts from drinking water. Copper-coated nano zero-valent iron (Cu-nZVI) bimetallic composites were synthesized to efficiently activate persulfate (PS) to remove nitrosopyrrolidine (NPYR). By introducing Cu-coated coatings, nZVI is protected from direct contact with PS; thus, Cu-nZVI appears to activate PS efficiently and stably without rapid deactivation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!