Neuron-astrocyte transmitophagy is altered in Alzheimer's disease

Lampinen, Riikka; Belaya, Irina; Saveleva, Liudmila; Liddell, Jeffrey R.; Rait, Dzhessi; Huuskonen, Mikko T; Giniatullina, Raisa; Sorvari, Annika; Soppela, Liisi; Mikhailov, Nikita; Boccuni, Isabella; Giniatullin, Rashid; Cruz-Haces, Marcela; Konovalova, Julia; Koskuvi, Marja; Domanskyi, Andrii; Hämäläinen, Riikka H.; Goldsteins, Gundars; Koistinaho, Jari; Malm, Tarja; Chew, Sweelin; Rilla, Kirsi; White, Anthony R.; Marsh-Armstrong, Nicholas

doi:10.1016/j.nbd.2022.105753

Cited by 51 publications

(30 citation statements)

References 49 publications

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“…In agreement with this scenario, astrocyte clearance of neuronal mitochondria is induced in co-cultured cells from AD mouse models, or iPSCs from symptomatic AD patients (Ref. 164), probably acting as compensatory mechanism, while the reduced capacity of astrocytes to execute transmitophagy has been suggested to participate in the pathogenesis of PD (Ref. 163).…”

Section: Mitophagy In Axonal Processesmentioning

confidence: 79%

The compartmentalised nature of neuronal mitophagy: molecular insights and implications

Borbolis

Palikaras

2022

Expert Rev. Mol. Med.

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The maintenance of a healthy mitochondrial network and the ability to adjust organelle population in response to internal or external stimuli are essential for the function and the survival of eukaryotic cells. Over the last two decades several studies have demonstrated the paramount importance of mitophagy, a selective form of autophagy that removes damaged and/or superfluous organelles, in organismal physiology. Post-mitotic neuronal cells are particularly vulnerable to mitochondrial damage, and mitophagy impairment has emerged as a causative factor in multiple neurodegenerative pathologies, including Alzheimer's disease and Parkinson's disease among others. Although mitochondrial turnover is a multifaceted process, neurons have to tackle additional complications, arising from their pronounced bioenergetic demands and their unique architecture and cellular polarisation that render the degradation of distal organelles challenging. Mounting evidence indicates that despite the functional conservation of mitophagy pathways, the unique features of neuronal physiology have led to the adaptation of compartmentalised solutions, which serve to ensure seamless mitochondrial removal in every part of the cell. In this review, we summarise the current knowledge concerning the molecular mechanisms that mediate mitophagy compartmentalisation and discuss their implications in various human pathologies.

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Section: Mitophagy In Axonal Processesmentioning

confidence: 79%

The compartmentalised nature of neuronal mitophagy: molecular insights and implications

Borbolis

Palikaras

2022

Expert Rev. Mol. Med.

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“…In vivo studies using artificial mitochondrial transplantation have also shown that astrocyte-derived mitochondria directly injected into the peri-infarct cortex of mice were present in neurons after 24 h [ 20 ]. Conversely, neurons have been shown to transfer damaged mitochondria to adjacent astrocytes in mouse primary neurons and astrocytes [ 31 , 32 , 33 ]. Intercellular mitochondrial transfer has also been observed between glia and other glia cells.…”

Section: Evidence Of Intercellular Mitochondrial Transfer In the Brainmentioning

confidence: 99%

“…Tunnelling nanotubes (TNTs) were first described in 2004 by Rustom and colleagues [ 42 ], who identified membranous channels comprised of F-actin that connect two or more cells and are involved in cell-to-cell communication [ 43 ]. TNTs were shown to transfer different organelles, including mitochondria, from one cell to another but also other cargo, including proteins (e.g., α-synuclein) and nucleotides [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Intercellular mitochondrial transfer via TNTs has been observed in astrocytes, microglia, and neurons.…”

Section: Structural Mechanisms Of Mitochondrial Transfermentioning

confidence: 99%

“…For instance, microglia have been shown to form a network of F-actin-positive intercellular membrane projections with neighbouring microglia that contain mitochondria [ 44 ]. TNT formation has also been observed between astrocytes and adjacent neurons in rat primary astrocyte and neuronal cells [ 33 , 45 , 46 , 47 ]. The direction of mitochondrial transfer between cells via TNTs is not fully understood; however, there is evidence to suggest that TNTs are formed in response to stress.…”

Section: Structural Mechanisms Of Mitochondrial Transfermentioning

confidence: 99%

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Mitochondria Transfer in Brain Injury and Disease

Fairley

Grimm

2022

Cells

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Intercellular mitochondria transfer is a novel form of cell signalling in which whole mitochondria are transferred between cells in order to enhance cellular functions or aid in the degradation of dysfunctional mitochondria. Recent studies have observed intercellular mitochondria transfer between glia and neurons in the brain, and mitochondrial transfer has emerged as a key neuroprotective mechanism in a range of neurological conditions. In particular, artificial mitochondria transfer has sparked widespread interest as a potential therapeutic strategy for brain disorders. In this review, we discuss the mechanisms and effects of intercellular mitochondria transfer in the brain. The role of mitochondrial transfer in neurological conditions, including neurodegenerative disease, brain injury, and neurodevelopmental disorders, is discussed as well as therapeutic strategies targeting mitochondria transfer in the brain.

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“…The release of damaged mitochondria might function as a help request to surrounding cells, triggering signaling pathways to restore homeostasis in the cell releasing damaged mitochondria ( 42 , 301 – 304 ). Mitochondrial transfer has been observed in a growing list of pathologies that include brain injury ( 42 , 309 ), neurodegenerative diseases ( 306 , 310 ), cancer ( 303 , 311 , 312 ), and cardiomyopathy ( 304 ). Mitochondria can be transferred from human synovial mesenchymal stem cells (sMSCs) to Th17 cells, which reduces the production of the pro-inflammatory cytokine IL-17.…”

Section: Targeting Mitochondrial Function: a Promising Approach For C...mentioning

confidence: 99%

Mitochondria and sensory processing in inflammatory and neuropathic pain

2022

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Rheumatic diseases, such as osteoarthritis and rheumatoid arthritis, affect over 750 million people worldwide and contribute to approximately 40% of chronic pain cases. Inflammation and tissue damage contribute to pain in rheumatic diseases, but pain often persists even when inflammation/damage is resolved. Mechanisms that cause this persistent pain are still unclear. Mitochondria are essential for a myriad of cellular processes and regulate neuronal functions. Mitochondrial dysfunction has been implicated in multiple neurological disorders, but its role in sensory processing and pain in rheumatic diseases is relatively unexplored. This review provides a comprehensive understanding of how mitochondrial dysfunction connects inflammation and damage-associated pathways to neuronal sensitization and persistent pain. To provide an overall framework on how mitochondria control pain, we explored recent evidence in inflammatory and neuropathic pain conditions. Mitochondria have intrinsic quality control mechanisms to prevent functional deficits and cellular damage. We will discuss the link between neuronal activity, mitochondrial dysfunction and chronic pain. Lastly, pharmacological strategies aimed at reestablishing mitochondrial functions or boosting mitochondrial dynamics as therapeutic interventions for chronic pain are discussed. The evidence presented in this review shows that mitochondria dysfunction may play a role in rheumatic pain. The dysfunction is not restricted to neuronal cells in the peripheral and central nervous system, but also includes blood cells and cells at the joint level that may affect pain pathways indirectly. Pre-clinical and clinical data suggest that modulation of mitochondrial functions can be used to attenuate or eliminate pain, which could be beneficial for multiple rheumatic diseases.

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Neuron-astrocyte transmitophagy is altered in Alzheimer's disease

Cited by 51 publications

References 49 publications

The compartmentalised nature of neuronal mitophagy: molecular insights and implications

The compartmentalised nature of neuronal mitophagy: molecular insights and implications

Mitochondria Transfer in Brain Injury and Disease

Mitochondria and sensory processing in inflammatory and neuropathic pain

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