1,721,039 research outputs found
Fanconi Anemia Genes, of Menders and Sweepers
Full text linkReporting recently in Cell, Sumpter et al. (2016) provide evidence that Fanconi anemia (FA) pathway genes, which are mutated in the homonymous disease and are tumor suppressors known as damaged nuclear DNA "menders," also act as intracellular sweepers in selective virophagy and mitophagy
Autophagy inhibition and mitochondrial remodeling join forces to amplify apoptosis in activation-induced cell death
Full text linkMitochondrial structural and functional changes and the autophagy pathway crosstalk under several stress conditions. However, their interplay under physiological cell death stimulation has been unclear. In our recent report, we show that during activation-induced cell death (AICD), the T-cell receptor (TCR)-dependent pathway that controls immune tolerance, autophagy is inhibited at an early stage. Further, we found that this inhibition is coupled with mitochondria fragmentation and cristae remodeling to unleash the apoptotic program. Last, we dissected the role of macroautophagy/autophagy versus mitophagy in the context of this physiological cell death, and bulk autophagy turned out to be able to remove dysfunctional and depolarized mitochondria. Our data suggest new possible approaches to modulate the immune function in the context of autoimmunity or immunotherapy
The mitochondrial pathway: Focus on shape changes
No full textMitochondria are key participants in cell death. They amplify death signals by releasing proapoptotic proteins normally stored in their intermembrane space, such as cytochrome c. In recent years, cytochrome c release has been demonstrated to be not only highly regulated by the proteins of the Bcl-2 family, but also influenced by changes in mitochondrial shape, including remodeling of the cristae and fragmentation of the cytosolic network, both orchestrated by a large group of mitochondria-shaping proteins. We focus our attention in this chapter on the involvement of mitochondrial shape changes in apoptosis and on their regulatory mechanisms. In particular, we discuss the roles of the pro-fusion OPA1 protein and of the inner mitochondrial membrane rhomboid PARL on cristae remodeling and apoptosis in mammals, and on the relationship among Bcl-2 family members, mitochondrial fragmentation, and cell death. These results open the possibility to modulate mitochondrial morphological changes in order to influence apoptosis and thus to intervene in the natural history of human diseases, from neurodegeneration to cancer
Monitoring the mitochondrial dynamics in mammalian cells
No full textMitochondria exist in a dynamic state inside mammalian cells. They undergo processes of fusion and fission to adjust their shape according to the different cell needs. Different proteins tightly regulate these dynamics: Opa-1 and Mitofusin-1 and Mitofusin-2 are the main profusion proteins, while Drp1 and its different receptors (Mff, Fis1, MiD49, MiD51) regulate mitochondrial fission. The dynamic nature of the mitochondrial network has become evident and detectable, thanks to recent advances in live imaging video microscopy and to the availability of mitochondria-tagged fluorescent proteins. High-resolution confocal reconstruction of mitochondria over time allows researchers to visualize mitochondria shape changes in living cells, under different experimental conditions. Moreover, in recent years, different techniques in living cells have been developed to study the process of mitochondria fusion in more details. Among them are fluorescence recovery after photobleaching (FRAP) of mitochondria-tagged GFP (mtGFP), use of photoactivatable mtGFP, polyethylene glycol (PEG)-based fusion of mtGFP and mtRFP cells, and Renilla luciferase assay (for population studies). In addition, in combination with imaging, the analysis of the expression levels of the different mitochondria-shaping proteins, along with that of their activation status, represents a powerful tool to investigate potential modulations of the mitochondrial network. Here, we review this aspect and then mention a number of techniques, with particular attention to their relative protocols
Mitochondrial Dynamics in Cancer and Neurodegenerative and Neuroinflammatory Diseases
Full text linkMitochondria are key organelles in the cell, hosting essential functions, from biosynthetic and metabolic pathways, to oxidative phosphorylation and ATP production, from calcium buffering to red-ox homeostasis and apoptotic signalling pathways. Mitochondria are also dynamic organelles, continuously fusing and dividing, and their localization, size and trafficking are finely regulated. Moreover, in recent decades, alterations in mitochondrial function and dynamics have been implicated in an increasing number of diseases. In this review, we focus on the relationship clarified hitherto between mitochondrial dynamics and cancer, neurodegenerative and neuroinflammatory diseases
Mitochondrial shape changes: orchestrating cell pathophysiology.
Full text linkMitochondria are highly dynamic organelles, the location, size and distribution of which are controlled by a family of proteins that modulate mitochondrial fusion and fission. Recent evidence indicates that mitochondrial morphology is crucial for cell physiology, as changes in mitochondrial shape have been linked to neurodegeneration, calcium signalling, lifespan and cell death. Because immune cells contain few mitochondria, these organelles have been considered to have only a marginal role in this physiological context-which is conversely well characterized from the point of view of signalling. Nevertheless, accumulating evidence shows that mitochondrial dynamics have an impact on the migration and activation of immune cells and on the innate immune response. Here, we discuss the roles of mitochondrial dynamics in cell pathophysiology and consider how studying dynamics in the context of the immune system could increase our knowledge about the role of dynamics in key signalling cascades
The Close interconnection between mitochondrial dynamics and mitophagy in cancer
Full text linkRecent decades have revealed the shape changes of mitochondria and their regulators to be main players in a plethora of physiological cell processes. Mitochondria are extremely dynamic organelles whose highly controlled morphological changes respond to specific and diverse pathophysiological needs. Thus, their qualitative control is crucial for the determination of cell function and fate. Moreover, ever-new metabolic changes, mainly attributable to mitochondrial (dys)functions, are strongly connected to cancer and its microenvironment. For this reason, the aspects controlling mitochondria activity and status are in the oncological spotlight. In this review, we elucidate the most intriguing discoveries related to two apparently independent but strictly interconnected processes crucial for the organelle functionality and fate, mitochondrial dynamics, and mitophagy. We will mostly focus on their metabolic interconnections and regulations that can causally foster a tumoral context
Recirculation and residency of T cells and tregs. lessons learnt in anacapri
Full text link“Location, location, and location”: according to this mantra, the place where living beings settle has a key impact on the success of their activities; in turn, the living beings can, in many ways, modify their environment. This idea has now become more and more true for T cells. The ability of T cells to recirculate throughout blood or lymph, or to stably reside in certain tissues, turned out to determine immunity to pathogens, and tumors. If location matters also for human beings, the inspiring environment of Capri Island has contributed to the success of the EFIS-EJI Ruggero Ceppellini Advanced School of Immunology focused on “T cell memory,” held in Anacapri from October 12, 2018 to October 15, 2018. In this minireview, we would like to highlight some novel concepts about T cell migration and residency and discuss their implications in relation to recent advances in the field, including the mechanisms regulating compartmentalization and cell cycle entry of T cells during activation, the role of mitochondrial metabolism in T cell movement, and the residency of regulatory T cells
Ho(a)xing autophagy to regulate development
Full text linkIn this issue of Developmental Cell, Banreti et al. (2014) demonstrate that canonical autophagy is inhibited in the Drosophila fat body by Hox transcriptional factors. This regulation involves repression of the Atg genes. Programmed developmental autophagy is thus under Hox control and may influence cell fate determination
The mitochondrial dynamics in cancer and immune-surveillance
Full text linkMitochondria-shaping proteins control the dynamic equilibrium between fusion and fission of the mitochondrial network. Their balance is strictly required to regulate various processes, including the quality of mitochondria, cell metabolism, cell death, proliferation and cell migration. Alterations in these processes are frequently encountered in cancer, during both its onset and later progression, as evidence emerge connecting alterations in mitochondrial dynamics with cancer development. In recent years, novel therapeutic approaches to fight against different human tumors aim at exploiting the immune system's ability to specifically recognize tumor antigens, thus killing malignant cells in a process named immune-surveillance. Interestingly, data are accumulating on the role that mitochondrial dynamics play also for the correct function of both the innate and the adaptive immune system. By this review, we overview how mitochondrial dynamics can affect various processes during cancer development, acting directly on tumor cells or indirectly on cells responsible for tumor aggression and defence
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