Mitochondria Regulate Inflammatory Paracrine Signalling in Neurodegeneration
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LETTER TO THE EDITOR
Mitochondria Regulate Inflammatory Paracrine Signalling in Neurodegeneration Danilo Faccenda 1 & Michelangelo Campanella 1,2 Received: 29 May 2020 / Accepted: 17 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Mitochondrial dysfunction occurs in most neurodegenerative diseases, contributing to both their onset and progression. A recent breakthrough unveiled that propagation of the inflammatory response and subsequent neuronal injury are also mediated extracellularly by damaged mitochondria, which are released from active microglial cells into the brain milieu. These extracellular fragmented mitochondria can therefore generate sufficient toxicity to trigger neuronal death and widespread brain damage through activation of naïve astrocytes. Besides suggesting potential new pharmacological strategies of therapeutic intervention in neurodegeneration, this original work indicates that mitochondria might act as bioactive ligands exerting paracrine functions. This is an interesting, novel and impactful concept that deserves consideration by the scientific community, as the attention should now be focused on the identification of the specific receptors through which mitochondria mediate such an important extracellular signalling mechanism in neurological conditions. Keywords Mitochondria . Extracellular signalling . Neurodegeneration
Dear Editor: Brain inflammation and neurodegenerative processes are intimately associated with mitochondrial dysfunction. With this letter, we would like to draw attention on a recent breakthrough revealing that extracellular damaged mitochondria can propagate the neuroinflammatory response and promote neuronal cell death (Joshi et al. 2019). In their work, Mochly-Rosen and colleagues establish that the release of fragmented mitochondria from activated microglial cells into the brain milieu is a pivotal event in neurodegenerative brain injury (Joshi et al. 2019). The group proposes that, once released, extracellular dysfunctional mitochondria trigger widespread brain damage through proinflammatory activation of naïve astrocytes (Joshi et al. 2019). This work widens the field of neuronal cell signalling and
* Michelangelo Campanella [email protected] 1
Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
2
Department of Cell and Developmental Biology, Consortium for Mitochondrial Research (CfMR), University College London, Gower Street, London WC1E 6BT, UK
suggests that mitochondria can act as bioactive ligands capable of paracrine properties. The extracellular release of mitochondria has recently emerged as a key mechanism mediating intercellular signalling between immune cells (e.g. monocytes, neutrophils and platelets) and has been implicated in diverse immune responses, including inflammatory signalling and adhesion of neutrophils to the vascular wall (Puhm et al. 2019, Boudreau et al. 2014, Houg et al. 2018). Although the concept o
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