About this Research Topic
Eukaryotic cells respond to environmental metabolic variations by establishing platforms in which membranes belonging to two, or more, organelles with specific metabolic activity, communicate one with the other and with the plasma membrane, through sophisticated inter-membrane junctions composed of unique proteomes and lipidomes. This allows the exchange of a variety of molecules (e.g., proteins, lipids, hormones, ions), including signalling molecules. The plastic assembly and disassembly of these physical tethers represent the mean by which different metabolisms are spatially and temporally coordinated to maintain cell homeostasis. Equally serving to the goal, organelles sealed by a phospholipid monolayer entertain close contacts with membrane-bound organelles, and apparently also membrane-less compartments that form by phase separation in different parts of the cell. Several circumstances, however, compromise such cross talks, resulting in deviation of organelles’ functions that in turn have detrimental impacts on the life of the cell.
Despite presenting high heterogeneous clinical and histopathological traits, neurodegenerative disorders share common features, including misfolding of proteins, synaptic dysfunction, and neuronal demise in the late stages of the diseases. No effective treatments have been available until now, which underscores the need for renewed efforts to clarify the molecular mechanisms of neural degeneration. Altered contact sites between organelles cause the development and progression of several diseases, including genetic and metabolic diseases. On this basis, and because reports have already disclosed that contact impairments may play a role, the present Research Topic (RT) aims to expand our knowledge on whether defective junctions are important players in the etiopathology of neurodegenerative disorders. To achieve this goal, the RT will need to comprise a clear picture of the established advancements on the cell metabolic integration by spatial proximity in both health and disease, and information on the many questions that, at least in part, remain unanswered. These include, for example, the full spectrum of the inter-organelle junction components; the mechanism underlying the sorting- and exchange-process of molecules and their ultimate fate; the cross-talk between membrane-bound and membrane-less compartments. Last but not the least, information, if available, on whether aberrant phase transitions or traits common to the diverse neurodegenerative types (e.g., accumulation of misfolded proteins, oxidative stress, Ca2+ dismetabolism), affect the spatiotemporal formation of metabolic platforms and lead to pathology.
The proposed RT aims at assessing the state of the art in the field, from the understanding of the molecular and structural organization of the highly specialized contact machineries to the exchanged molecules and their action under physiological and neuro-pathological conditions. This is important as a way to design targeted pharmaceutical interventions and tools for early diagnosis. Reviews articles describing the advancement achieved in these different aspects are welcome. At the same time, the RT seeks original contributions reporting novel information regarding metabolite exchanges in physiology or occurring in neurodegenerative disorders that will provide important insight, and stimuli to focussed research, into the diverse age-related pathologies.
Keywords: Contact sites, Cell homeostasis, Membrane-bound organelles, Membrane-less compartments, Phase separation, Signalling, Neurodegeneration, Neurodegenerative Disorder
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