NAD(H) Regulates the Permeability Transition Pore in Mitochondria through an External Site

Kharechkina, Ekaterina S.; Nikiforova, Anna B.; Kruglov, Alexey G.

doi:10.3390/ijms22168560

Cited by 10 publications

(8 citation statements)

References 64 publications

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“…Presently, it remains uncertain whether the voltage-dependent anion channel, Adinosine nucleotide translocase, or even the outer mitochondrial membrane are integral components of PTP for channel formation (Kim, et. al., 2023, Kharechkina, et. al., 2023.…”

Section: The Role Of Endoplasmic Reticulum and Mitochondria In Progra...mentioning

confidence: 99%

Signaling Pathway Governed by Lipid Derived Molecules as Secondary Messenger

Kundu,

Halder

2024

IJALSR

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Research shown that the cell death, particularly apoptosis, can extend beyond single cell boundaries. Gap junctions IP3 diffusion, and sphingolipids play significant roles in membrane biology and regulation of cell function. S1P plays crucial role in the cardiovascular and immune systems, serving as a mediator of signaling during cell migration, differentiation, proliferation, and apoptosis. Intestinal phospholipid metabolism, including 1B phospholipase A2 and autotaxin-mediated pathways, contributes to cardiometabolic diseases through multiple mechanisms. A potential strategy for treating cardiovascular and metabolic diseases is the therapeutic suppression of1B phospholipase A2 and autotaxin in the gastrointestinal tract. Cellular stress signalling, inflammation, resolution, and host defence responses are all significantly influenced by lysophospholipids such LPA and S1P. New therapies for cancer, vascular diseases, fibrotic disorders, and autoimmune diseases have been made possible by developments in lysophospholipid research.

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Section: The Role Of Endoplasmic Reticulum and Mitochondria In Progra...mentioning

confidence: 99%

Signaling Pathway Governed by Lipid Derived Molecules as Secondary Messenger

Kundu,

Halder

2024

IJALSR

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“…Thus, it seems that NAD + precursors offer novel opportunities for acute protection against cardiac IRI. Although studies in isolated mitochondria have suggested protection through direct inhibition of mPTP by NAD + [75], studies in intact hearts or in vivo favor activation of glycolysis as the major protective mechanism of these compounds.…”

Section: Nad + Precursorsmentioning

confidence: 99%

Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy

Wang,

Zuurbier,

Huhn

et al. 2023

Cells

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Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆GATP, Na+, Ca2+, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH4, and NAD+). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca2+ overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition.

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“…It plays a crucial role in maintaining mitochondrial homeostasis, regulating cell death pathways, and controlling mitochondrial function. [1–3] When the mPTP opens excessively, it leads to mitochondrial dysfunction, oxidative stress, and cell death. [4,5] Acute pancreatitis is an inflammatory condition characterized by the sudden inflammation of the pancreas.…”

Section: Introductionmentioning

confidence: 99%

Rational design peptide inhibitors of Cyclophilin D as a potential treatment for acute pancreatitis

Li,

Liu,

Lai

et al. 2023

Medicine

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Cyclophilin D (CypD) is a mitochondrial matrix peptidyl prolidase that regulates the mitochondrial permeability transition pore. Inhibition of CypD was suggested as a therapeutic strategy for acute pancreatitis. Peptide inhibitors emerged as novel binding ligand for blocking receptor activity. In this study, we present our computational approach for designing peptide inhibitors of CypD. The 3-D structure of random peptides were built, and docked into the active center of CypD using Rosetta script integrated FlexPepDock module. The peptide displayed the lowest binding energy against CypD was further selected for virtual iterative mutation based on virtual mutagenesis and molecular docking. Finally, the top 5 peptides with the lowest binding energy was selected for validating their affinity against CypD using inhibitory assay. We showed 4 out of the selected 5 peptides were capable for blocking the activity of CypD, while WACLQ display the strongest affinity against CypD, which reached 0.28 mM. The binding mechanism between WACLQ and CypD was characterized using molecular dynamics simulation. Here, we proved our approach can be a robust method for screening peptide inhibitors.

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NAD(H) Regulates the Permeability Transition Pore in Mitochondria through an External Site

Cited by 10 publications

References 64 publications

Signaling Pathway Governed by Lipid Derived Molecules as Secondary Messenger

Signaling Pathway Governed by Lipid Derived Molecules as Secondary Messenger

Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy

Rational design peptide inhibitors of Cyclophilin D as a potential treatment for acute pancreatitis

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