Ca2+ signaling and cell death

Cell Calcium, Journal Year: 2023, Volume and Issue: 113, P. 102759 - 102759

Published: May 19, 2023

Multiple forms of regulated cell death (RCD) have been characterized, each which originates from the activation a dedicated molecular machinery. RCD can occur in purely physiological settings or upon failing cellular adaptation to stress. Ca2+ions shown physically interact with - and hence regulate various components Moreover, intracellular Ca2+ accumulation promote organellar dysfunction degree that be overtly cytotoxic sensitize cells elicited by other stressors. Here, we provide an overview main links between Ca2+and different RCD, including apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, lysosome-dependent death, parthanatos.

Language: Английский

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Folate-modified carboxymethyl chitosan-based drug delivery system for breast cancer specific combination therapy via regulating mitochondrial calcium concentration

Carbohydrate Polymers, Journal Year: 2023, Volume and Issue: 323, P. 121434 - 121434

Published: Sept. 26, 2023

Language: Английский

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ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Oct. 10, 2024

IP

Language: Английский

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The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: June 8, 2023

Introduction: The mitochondrial uniporter (MCU) Ca2+ ion channel represents the primary means for uptake by mitochondria. Mitochondrial matrix plays critical roles in bioenergetics impinging upon respiration, energy production and flux of biochemical intermediates through TCA cycle. Inhibition MCU oncogenic cell lines results an energetic crisis reduced proliferation unless media is supplemented with nucleosides, pyruvate or α-KG. Nevertheless, MCU-mediated influx cancer cells remain unclear, part because a lack genetic models. Methods: was genetically deleted transformed murine fibroblasts study vitro vivo. Tumor formation growth were studied xenograft Proliferation, invasion, spheroid cycle progression measured vitro. effects deletion on survival cell-death determined probing live/death markers. measuring concentration, membrane potential, global dehydrogenase activity, ROS inactivating-phosphorylation dehydrogenase. rescue metabolism examined tracing glucose glutamine utilization fueling respiration. Results: Transformation associated increased expression, enhanced uptake, altered concentration responses to agonist stimulation, suppression modest increase Genetic inhibited HEK293T mouse models, delayed cell-cycle progression. stem cell-like invasion vitro, both predictors metastatic potential. Surprisingly, [Ca2+], respiration unaffected. In contrast, elevated glycolysis glutaminolysis, strongly sensitized limitation, agonist-induced cytoplasmic signals. Conclusion: Our reveal dependence tumorigenesis MCU, mediated reliance dynamics necessary proliferation.

Language: Английский

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Molecular determinants of immunogenic cell death elicited by radiation therapy

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 20 - 32

Published: Sept. 7, 2023

Summary Cancer cells undergoing immunogenic cell death (ICD) can initiate adaptive immune responses against dead cell‐associated antigens, provided that (1) said antigens are not perfectly covered by central tolerance (antigenicity), (2) occurs along with the emission of immunostimulatory cytokines and damage‐associated molecular patterns (DAMPs) actively engage effector mechanisms (adjuvanticity), (3) microenvironment dying is permissive for initiation immunity. Finally, ICD‐driven only operate exert cytotoxic functions if target cancer enables infiltration activity. Multiple forms radiation, including non‐ionizing (ultraviolet) ionizing elicit bona fide ICD as they increase both antigenicity adjuvanticity cells. Here, we review determinants elicited radiation critically discuss strategies to reinforce immunogenicity succumbing clinically available strategies.

Language: Английский

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Mitochondria-associated membrane protein PACS2 maintains right cardiac function in hypobaric hypoxia

iScience, Journal Year: 2023, Volume and Issue: 26(4), P. 106328 - 106328

Published: March 5, 2023

Hypobaric hypoxia (HH) is the primary challenge at highland. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxia, but mechanism was unclear. In this study, proteomics analysis identified that PACS2, key protein MAM, and mitophagy were downregulated HH. Metabolomics indicated suppression of glucose fatty acids aerobic oxidation conditions. Cardiomyocyte Pacs2 deficiency disrupted MAM formation endoplasmic reticulum (ER)-mitochondria calcium flux, further inhibiting energy metabolism overexpression reversed these effects. Cardiac-specific knockout exacerbated inhibition, cardiomyocyte injury, dysfunction induced by Conditional knock-in recovered HH-induced impairment. Thus, PACS2 essential for protecting cardiomyocytes through ER-mitochondria mitophagy, metabolism. Our work provides insight into injury potential targets maintaining

Language: Английский

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Fundamental Role of Pentose Phosphate Pathway within the Endoplasmic Reticulum in Glutamine Addiction of Triple-Negative Breast Cancer Cells

Antioxidants, Journal Year: 2022, Volume and Issue: 12(1), P. 43 - 43

Published: Dec. 26, 2022

Cancer utilization of large glutamine equivalents contributes to diverging glucose-6-P flux toward the pentose phosphate shunt (PPP) feed building blocks and antioxidant responses rapidly proliferating cells. In addition well-acknowledged cytosolic pathway, cancer cells also run a largely independent PPP, triggered by hexose-6P-dehydrogenase within endoplasmic reticulum (ER), whose activity is mandatory for integrity ER–mitochondria networking. To verify whether this reticular metabolism dependent on levels, we complemented metabolomic characterization intermediates glucose tricarboxylic acid cycle with estimation activity, energy metabolism, redox damage, mitochondrial function in two breast cell lines. ER-PPP its determinants were estimated ER accumulation analogs. Glutamine shortage decreased proliferation rate despite increased ATP NADH levels. It depleted NADPH reductive power malondialdehyde content marked increase glucose-6P-dehydrogenase. This paradox was explained deceleration favored decrease expression coupled opposite response competitor enzyme glucose-6P-phosphatase. The eventually hampered calcium exchanges. These data configure as powerful, unrecognized regulator proliferation.

Language: Английский

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Autophagy-inducing nutritional interventions in experimental and clinical oncology

International review of cell and molecular biology, Journal Year: 2022, Volume and Issue: unknown, P. 125 - 158

Published: Jan. 1, 2022

Language: Английский

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Structural basis of Ca²⁺ uptake by mitochondrial calcium uniporter in mitochondria: a brief review

BMB Reports, Journal Year: 2022, Volume and Issue: 55(11), P. 528 - 534

Published: Nov. 30, 2022

Other SectionsABSTRACTINTRODUCTIONMCU, ACTS AS A Ca2+ CHANNEL THAT CAN CONTROL THEIR ACTIVITY BY THEMSELVESEMRE, THE ESSENTIAL PIECE FOR ION PERMEATION MCUTHE MCU HOLO-COMPLEX CONTROLS UPTAKE SOPHISTICATEDLY THROUGH ITS SUBUNITSDISCUSSIONACKNOWLEDGEMENTSCONFLICTS OF INTERESTFIGURESREFERENCES

Language: Английский

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Emerging and Novel Therapeutic Treatments Targeting Mitochondrial-Endoplasmic Reticulum Contact Sites in Metabolic and Vascular Disorders

International Journal of Drug Discovery and Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 100008 - 100008

Published: June 6, 2024

Review Emerging and Novel Therapeutic Treatments Targeting Mitochondrial-Endoplasmic Reticulum Contact Sites in Metabolic Vascular Disorders Richard M. Monaghan The British Heart Foundation Centre of Research Excellence Manchester, Division Cardiovascular Sciences, Faculty Biology, Medicine, Health, University AV Hill Building, Oxford Road, M13 9PN, UK;[email protected] Received: 10 April 2024; Revised: 5 May Accepted: 7 Published: 6 June 2024 Abstract: Subcellular organellar contact sites, particularly those between mitochondria the endoplasmic reticulum (MERCSs), play crucial roles maintaining health. These specialized partitions facilitate vital communication organelles, regulating processes essential for cell function, including calcium balance, lipid biogenesis transport, mitochondrial dynamics, programmed death. Growing evidence shows that perturbation MERCSs contributes significantly to various diseases, neurodegenerative disorders like Alzheimer’s Parkinson’s, metabolic issues, such as type 2 diabetes, heart conditions, cancer. This review dives into this expanding field, exploring potential therapeutic targets. It provides a detailed overview proteins form maintain MERCSs, highlighting how their disruption can lead cellular dysfunction disease. Additionally, it examines recent exciting breakthroughs developing drugs strategies manipulate clinical benefits. While challenges remain, emphasises MERCS-based therapies outlines critical research needed move these treatments from lab clinic.

Language: Английский

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