Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹

Autophagy, Год журнала: 2021, Номер 17(1), С. 1 - 382

Опубликована: Янв. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Язык: Английский

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Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(21), С. 8323 - 8323

Опубликована: Ноя. 6, 2020

Calcium (Ca2+) is a major second messenger in cells and essential for the fate survival of all higher organisms. Different Ca2+ channels, pumps, or exchangers regulate variations duration levels intracellular Ca2+, which may be transient sustained. These changes are then decoded by an elaborate toolkit Ca2+-sensors, translate signal to operational cell machinery, thereby regulating numerous Ca2+-dependent physiological processes. Alterations homoeostasis signaling often deleterious associated with certain pathological states, including cancer. Altered transmission has been implicated variety processes fundamental uncontrolled proliferation invasiveness tumor other important cancer progression, such as development resistance therapies. Here, we review what known about how this regulates life death decisions context cancer, particular attention directed proliferation, apoptosis, autophagy. We also explore intersections therapeutic targeting cells, summarizing opportunities modulators improve effectiveness current anticancer

Язык: Английский

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Ca2+ Fluxes and Cancer

Molecular Cell, Год журнала: 2020, Номер 78(6), С. 1055 - 1069

Опубликована: Июнь 1, 2020

Язык: Английский

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Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy

Nano-Micro Letters, Год журнала: 2022, Номер 14(1)

Опубликована: Июль 18, 2022

As the indispensable second cellular messenger, calcium signaling is involved in regulation of almost all physiological processes by activating specific target proteins. The importance ions (Ca

Язык: Английский

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Triggers, cascades, and endpoints: connecting the dots of coral bleaching mechanisms

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Год журнала: 2024, Номер 99(3), С. 715 - 752

Опубликована: Янв. 12, 2024

ABSTRACT The intracellular coral–dinoflagellate symbiosis is the engine that underpins success of coral reefs, one most diverse ecosystems on planet. However, breakdown and loss microalgal symbiont (i.e. bleaching) due to environmental changes are resulting in rapid degradation reefs globally. There an urgent need understand cellular physiology bleaching at mechanistic level help develop solutions mitigate reef crisis. Here, unprecedented scope, we present novel models integrate putative mechanisms within a common framework according triggers (initiators bleaching, e.g. heat, cold, light stress, hypoxia, hyposalinity), cascades (cellular pathways, photoinhibition, unfolded protein response, nitric oxide), endpoints (mechanisms loss, apoptosis, necrosis, exocytosis/vomocytosis). supported by direct evidence from cnidarian systems, indirectly through comparative evolutionary analyses non‐cnidarian systems. With this approach, new have been established between initiated different triggers. In particular, provide insights into poorly understood connections highlight role mechanism i.e. ‘symbiolysosomal digestion’, which symbiophagy. This review also increases approachability for specialists non‐specialists mapping vast landscape atlas comprehensible detailed models. We then discuss major knowledge gaps how future research may improve understanding cascade pathways (endpoints).

Язык: Английский

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Metal Ion Signaling in Biomedicine

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.

Язык: Английский

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The Molecular Biology of Placental Transport of Calcium to the Human Foetus

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 383 - 383

Опубликована: Янв. 4, 2025

From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca2+ transfers. In addition, from around eighth week of gestation, increasing amounts routed directly maternal blood foetus bone mineralisation through a flow-through system, which does not impact concentration. These different processes are mediated by numerous membrane-sited channels, transporters, exchangers. Understanding mechanisms is essential direct interventions optimise foetal development postnatal health protect mother pre-eclampsia. Ethical issues limit availability human tissue study. Our insight placental handling advancing rapidly, enabled developing genetic, analytical, computer technology. Because their diverse sources, reports new findings scattered. review aims pull data together highlight areas uncertainty. Areas needing clarification include trafficking, membrane expression, recycling channels transporters in microvilli; metabolism vitamin D gestational diabetes pre-eclampsia; vascular effects increased endothelial Orai expression pregnancy-specific beta-1-glycoproteins PSG1 PSG9.

Язык: Английский

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Bcl-xL acts as an inhibitor of IP3R channels, thereby antagonizing Ca2+-driven apoptosis

Cell Death and Differentiation, Год журнала: 2021, Номер 29(4), С. 788 - 805

Опубликована: Ноя. 8, 2021

Abstract Anti-apoptotic Bcl-2-family members not only act at mitochondria but also the endoplasmic reticulum, where they impact Ca 2+ dynamics by controlling IP 3 receptor (IP R) function. Current models propose distinct roles for Bcl-2 vs. Bcl-xL, with inhibiting Rs and preventing pro-apoptotic release Bcl-xL sensitizing to low [IP ] promoting pro-survival oscillations. We here demonstrate that too inhibits R-mediated interacting same R regions as Bcl-2. Via in silico superposition, we previously found residue K87 of spatially resembled K17 Bcl-2, a critical Bcl-2’s R-inhibitory properties. Mutagenesis impaired its binding abrogated Bcl-xL’s inhibitory effect on Rs. Single-channel recordings purified K87D , suppressed single-channel openings stimulated sub-maximal threshold ]. Moreover, Bcl-xL-mediated inhibition contributes anti-apoptotic properties against -driven apoptosis. Staurosporine (STS) elicits long-lasting elevations wild-type R-knockout HeLa cells, former STS treatment. Overexpression cells STS-induced signals cell death, while was much less effective doing so. In absence Rs, were equally suppressing death. Finally, endogenous suppress activity MDA-MB-231 breast cancer whereby knockdown augmented increased sensitivity towards STS, without altering ER content. Hence, this study challenges current paradigm divergent functions -signaling modulation reveals that, similarly R-driven Our work further underpins is an integral part

Язык: Английский

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A comprehensive overview of the complex world of the endo- and sarcoplasmic reticulum Ca2+-leak channels

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2021, Номер 1868(7), С. 119020 - 119020

Опубликована: Март 30, 2021

Язык: Английский

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The role of Bcl-2 proteins in modulating neuronal Ca2+ signaling in health and in Alzheimer's disease

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2021, Номер 1868(6), С. 118997 - 118997

Опубликована: Март 9, 2021

Язык: Английский

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