Seminars in Cell and Developmental Biology, Год журнала: 2019, Номер 94, С. 59 - 65
Опубликована: Янв. 30, 2019
Язык: Английский
Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 27, 2025
Язык: Английский
Процитировано
5
The FASEB Journal, Год журнала: 2019, Номер 33(12), С. 13176 - 13188
Опубликована: Сен. 4, 2019
Changes in mitochondrial size and shape have been implicated several physiologic processes, but their role Ca2+ uptake regulation overall cellular homeostasis is largely unknown. Here we show that modulating dynamics toward increased fusion through expression of a dominant negative (DN) form the fission protein [dynamin-related 1 (DRP1)] markedly both retention capacity rates permeabilized C2C12 cells. Similar results were seen using pharmacological fusion-promoting M1 molecule. Conversely, promoting phenotype knockdown mitofusin (MFN)-2 strongly reduced speed these These changes not dependent on modifications calcium uniporter expression, inner membrane potentials, or permeability transition. Implications morphology modulation measured intact cells; promoted lower basal levels endoplasmic reticulum (ER) stores, as indicated by depletion with thapsigargin. Indeed, was associated ER stress. Additionally, calcium-replenishing process store-operated entry impaired MFN2 cells, whereas DRP1-DN-promoted resulted faster cytosolic increase rates. Overall, our novel for uptake, which impacts homeostasis.-Kowaltowski, A. J., Menezes-Filho, S. L., Assali, E. A., Gonçalves, I. G., Cabral-Costa, J. V., Abreu, P., Miller, N., Nolasco, Laurindo, F. R. M., Bruni-Cardoso, Shirihai, O. Mitochondrial regulates organellar homeostasis.
Язык: Английский
Процитировано
117
Frontiers in Cell and Developmental Biology, Год журнала: 2019, Номер 7
Опубликована: Дек. 19, 2019
Mitochondria in addition to being a main cellular power station, are involved the regulation of many physiological processes, such as generation reactive oxygen species, metabolite production and maintenance intracellular Ca2+ homeostasis. Almost 100 years ago Otto Warburg presented evidence for role mitochondria development cancer. Over past 20 mitochondrial involvement programmed cell death has become clear. Moreover, it been shown that may act switchboard between various modalities. Recently, accumulated data have pointed metastatic dissemination cancer cells. Here we summarize modern knowledge concerning contribution invasion tumor cells possible mechanisms behind attempt target cancers involving mitochondria.
Язык: Английский
Процитировано
109
Cells, Год журнала: 2020, Номер 9(2), С. 432 - 432
Опубликована: Фев. 12, 2020
Calcium (Ca2+) uptake into the mitochondria shapes cellular Ca2+ signals and acts as a key effector for ATP generation. In addition, mitochondria-derived reactive oxygen species (mROS), produced consequence of synthesis at electron transport chain (ETC), modulate signaling pathways that contribute to many processes. Cancer cells mitochondrial ([Ca2+]m) homeostasis by altering expression function channels transporters required extrusion Ca2+. Regulated elevations in [Ca2+]m are activity several enzymes, this turn regulates metabolic flux, ETC mROS Alterations both hallmarks tumors, elevated is known driver pro-tumorigenic redox signaling, resulting activation implicated proliferation, alterations stress-adaptations. review, we highlight recent studies demonstrate interplay between cancer.
Язык: Английский
Процитировано
106
Cell Calcium, Год журнала: 2020, Номер 91, С. 102281 - 102281
Опубликована: Авг. 29, 2020
Язык: Английский
Процитировано
85
Annual Review of Physiology, Год журнала: 2021, Номер 84(1), С. 355 - 379
Опубликована: Окт. 12, 2021
Store-operated Ca 2+ entry (SOCE) is a ubiquitous signaling pathway that evolutionarily conserved across eukaryotes. SOCE triggered physiologically when the endoplasmic reticulum (ER) stores are emptied through activation of inositol 1,4,5-trisphosphate receptors. mediated by release-activated (CRAC) channels, which highly selective. Upon store depletion, ER -sensing STIM proteins aggregate and gain extended conformations spanning ER–plasma membrane junctional space to bind activate Orai, pore-forming hexameric CRAC channels. In recent years, studies on Orai tissue-specific knockout mice gain- loss-of-function mutations in humans have shed light physiological functions various tissues. Here, we describe findings composition native channels their immune, muscle, secretory, neuronal systems draw lessons from transgenic human diseases caused altered channel activity.
Язык: Английский
Процитировано
82
Experimental Physiology, Год журнала: 2017, Номер 103(2), С. 157 - 169
Опубликована: Дек. 6, 2017
What is the topic of this review? This paper overviews links between Ca2+ and Na+ signalling in various types cells. advances does it highlight? highlights general importance ionic molecular mechanisms linking dynamics. In particular, narrative focuses on physiology plasmalemmal mitochondrial -Ca2+ exchangers transient receptor potential channels. Functional consequences for co-ordination neuronal activity with astroglial homeostatic pathways fundamental synaptic transmission are discussed.Transmembrane gradients, which an indispensable feature life, used generation cytosolic signals that regulate a host cellular functions. Intracellular mediated by tightly linked through several generate fluxes turn regulated both ions. Transient (TRP) channels bridge endoplasmic reticulum release currents. The exchanger (NCX) flickers forward reverse mode to co-ordinate influx efflux ions membrane polarization ion concentrations. calcium uniporter channel (MCU) (NCLX) mediate entry into from organelle couple fluctuations energetics. Cellular controls numerous functional responses and, CNS, provides fast regulation cascades crucial maintenance transmission.
Язык: Английский
Процитировано
75
Cell Death and Disease, Год журнала: 2018, Номер 9(3)
Опубликована: Фев. 28, 2018
Abstract Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are dynamic modules enriched in subset of lipids specialized proteins that determine their structure functions. The MERCs regulate lipid transfer, autophagosome formation, mitochondrial fission, Ca 2+ homeostasis apoptosis. Since these functions essential for cell biology, it is therefore not surprising also play a critical role organ physiology among which the immune system stands by its host defense function. This must discriminate tolerate cells beneficial commensal microorganisms while eliminating pathogenic ones order to preserve normal homeostasis. To meet this goal, has two lines defense. First, fast acting but unspecific innate relies on anatomical physical barriers subsets hematopoietically derived expressing germline-encoded receptors called pattern recognition (PRR) recognizing conserved motifs pathogens. Second, slower very specific adaptive response added complement immunity. Adaptive immunity another set cells, lymphocytes, harboring requiring somatic recombination be expressed. Both activated phagocytose process pathogens, migrate, proliferate, release soluble factors destroy infected cells. Some strongly dependent flux; indicates could
Язык: Английский
Процитировано
68
eLife, Год журнала: 2020, Номер 9
Опубликована: Сен. 11, 2020
Despite the established role of mitochondria in cancer, mechanisms by which mitochondrial Ca2+ (mtCa2+) regulates tumorigenesis remain incompletely understood. The crucial mtCa2+ is highlighted altered expression proteins mediating uptake and extrusion cancer. Here, we demonstrate decreased Na+/Ca2+/Li+ exchanger NCLX (SLC8B1) human colorectal tumors its association with advanced-stage disease patients. Downregulation causes overload, depolarization, cell-cycle genes reduced tumor size xenograft spontaneous cancer mouse models. Concomitantly, downregulation drives metastatic spread, chemoresistance, epithelial-to-mesenchymal, hypoxia, stem cell pathways. Mechanistically, overload leads to increased reactive oxygen species, activate HIF1α signaling supporting metastasis NCLX-null cells. Thus, loss a novel driver metastasis, indicating that regulation therapeutic approach cancer.Colorectal second largest cause deaths worldwide. Even cases where diagnosed treated early, cells can sometimes survive treatment spread other organs. Once has survival rate less than 15%. Mitochondria are compartments produce energy, they play an important rapid growth levels calcium ions control how process To better understand influence growth, Pathak, Gueguinou et al. studied protein called NCLX, controls pumping them out mitochondria. Two strains were used study what happens if missing. first strain was genetically modified disable gene for then exposed carcinogens. injected from lacking NCLX. In both strains, formed smaller mice However, model more likely This because build-up led increase production hypoxia-inducible factor-1a, common spread. demonstrated affect progression. It suggests it may have opposing effects during early late-stage encouraging but also decreasing Further research could help refine treatments at different stages disease.
Язык: Английский
Процитировано
54
International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4770 - 4770
Опубликована: Апрель 30, 2021
Mitochondria are key regulators of cell survival and involved in a plethora mechanisms, such as metabolism, Ca2+ signaling, reactive oxygen species (ROS) production, mitophagy mitochondrial transfer, fusion, fission (known dynamics). The tuning these processes pathophysiological conditions is fundamental to the balance between death survival. Indeed, ROS overproduction overload linked induction apoptosis, while impairment dynamics metabolism can have double-faceted role decision death. Tumorigenesis involves an intricate series cellular impairments not yet completely clarified, further level complexity added by onset apoptosis resistance mechanisms cancer cells. In majority cases, relapse or lack responsiveness related emergence chemoresistance, which may be due cooperation several protection often mitochondria-related. With this review, we aim critically report current evidence on relationship mitochondria chemoresistance with particular focus involvement dynamics, oxidative stress, possibly identify new approaches targets for overcoming resistance.
Язык: Английский
Процитировано
52