Ischemia-reperfusion injury remains a major clinical problem in liver transplantation. One contributing factor is mitochondrial calcium (mCa(2+)) overload, which triggers apoptosis; calcium also regulates mitochondrial respiration and adenosine 5'-triphosphate (ATP) production. Recently, we reported the presence of purinergic P2Y(1)- and P2Y(2)-like receptor proteins in mitochondrial membranes. Herein, we present an evaluation of the functional characteristics of these receptors. In experiments with isolated mitochondria, specific P2Y(1) and P2Y(2) receptors ligands: 2-methylthio-adenosine 5'-diphosphate (2meSADP) and uridine 5'-triphosphate (UTP), respectively, were used, and mitochondrial calcium uptake was measured. 2meSADP and UTP had a maximum effect at concentrations in the range of the known P2Y(1) and P2Y(2) receptors. The P2Y inhibitor phosphate-6-azophenyl-2',4'-disulfonate (PPADS) blocked the effects of both ligands. The phospholipase C (PLC) antagonist U73122 inhibited the effect of both ligands while its inactive analog U73343 had no effect. These data strongly support the hypothesis that mitochondrial Ca(2+) uptake is regulated in part by adenine nucleotides via a P2Y-like receptor mechanism that involves mitochondrial PLC activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jcb.20985 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Biochanin a modulates steroidogenesis and cellular metabolism in human granulosa cells through TAS2Rs activation: a spotlight on ovarian function.
Reprod Biol Endocrinol
January 2025
Department of Molecular and Developmental Medicine, Siena University, Siena, 53100, Italy.
Background: Endocrine-disrupting chemicals (EDCs) interfere with the endocrine system and negatively impact reproductive health. Biochanin A (BCA), an isoflavone with anti-inflammatory and estrogen-like properties, has been identified as one such EDC. This study investigates the effects of BCA on transcription, metabolism, and hormone regulation in primary human granulosa cells (GCs), with a specific focus on the activation of bitter taste receptors (TAS2Rs).
View Article and Find Full Text PDFEvaluation of transcriptomic changes after photobiomodulation in spinal cord injury.
Sci Rep
January 2025
Neuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Spinal cord injury (SCI) is a significant cause of lifelong disability, with no available disease-modifying treatments to promote neuroprotection and axon regeneration after injury. Photobiomodulation (PBM) is a promising therapy which has proven effective at restoring lost function after SCI in pre-clinical models. However, the precise mechanism of action is yet to be determined.
View Article and Find Full Text PDFMechanisms of dual modulatory effects of spermine on the mitochondrial calcium uniporter complex.
J Biol Chem
January 2025
Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22903. Electronic address:
The mitochondrial Ca uniporter is the Ca channel responsible for mitochondrial Ca uptake. It plays crucial physiological roles in regulating oxidative phosphorylation, intracellular Ca signaling, and cell death. The uniporter contains the pore-forming MCU subunit, the auxiliary EMRE protein, and the regulatory MICU1 subunit, which blocks the MCU pore under resting cellular Ca concentrations.
View Article and Find Full Text PDFYou better keep an eye on your contacts.
Cell Calcium
January 2025
Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Membrane contact sites (MCS) are specialized compartments found in all eukaryotic cells that are formed between membranes of different organelles that are in close proximity. MCS have important functions as they are sites of efficient transfer of molecules between neighboring organelles. Two recent articles have used the splitFAST system to mark and follow the dynamics of membrane contact sites and used the method to highlight the importance of MCS between the endoplasmic reticulum (ER) and lipid droplets in metabolic adaptation and MCS between the ER and mitochondria in Ca signal propagation.
View Article and Find Full Text PDFMitochondria as a Therapeutic Target: Focusing on Traumatic Brain Injury.
J Integr Neurosci
January 2025
Department of Hepatology, Federal University of Health Sciences of Porto Alegre (UFCSPA), 90050-170 Porto Alegre, Rio Grande do Sul (RS), Brazil.
Mitochondria are organelles of eukaryotic cells delimited by two membranes and cristae that consume oxygen to produce adenosine triphosphate (ATP), and are involved in the synthesis of vital metabolites, calcium homeostasis, and cell death mechanisms. Strikingly, normal mitochondria function as an integration center between multiple conditions that determine neural cell homeostasis, whereas lesions that lead to mitochondrial dysfunction can desynchronize cellular functions, thus contributing to the pathophysiology of traumatic brain injury (TBI). In addition, TBI leads to impaired coupling of the mitochondrial electron transport system with oxidative phosphorylation that provides most of the energy needed to maintain vital functions, ionic homeostasis, and membrane potentials.
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!