Mitochondria Transfer in Brain Injury and Disease
Abstract
:1. Introduction
2. Evidence of Intercellular Mitochondrial Transfer in the Brain
3. Structural Mechanisms of Mitochondrial Transfer
3.1. Extracellular Vesicles
3.2. Tunneling Nanotubes
3.3. Other Mechanisms
Method of Transfer | Cell Type | Disease Model/Stressor | Effects of Mito Transfer | Ref. | ||
---|---|---|---|---|---|---|
Donor | Recipient | Donor | Recipient | |||
EVs | Neural stem cells | BMDM | LPS | N/A | -Increased mitochondrial fusion | [56] |
-Increased cellular respiration | ||||||
-Reduced inflammatory gene profiles | ||||||
EVs | Primary human | N/A | ATP released from neighbouring cells | N/A | N/A | [39] |
Astrocytes | ||||||
EVs | Primary rat astrocytes | Primary rat neurons | Oxygen-glucose deprivation | N/A | -Increase ATP levels | [20] |
-Increased cell viability | ||||||
TNTs | PC12 cells | PC12 cells | UV light | N/A | -Decreased apoptosis | [48] |
TNTs | MMSC | Primary astrocytes | Oxygen-glucose deprivation | -Increased transfer | -Restored bioenergetics | [49] |
and | -Increased proliferation | |||||
PC12 cells | ||||||
TNTs | MSC | Neural stem cells | Cisplatin | N/A | -Decreased apoptosis | [50] |
-Increased MMP | ||||||
TNTs | Primary mouse astrocytes | Primary mouse neurons | Compressed nitrogen–oxygen mixed gas | N/A | -Increased dendrite length | [19] |
-Increased transcription of mitochondrial synthesis-related genes | ||||||
TNTs | Primary mouse microglia | Primary mouse microglia | α-syn | N/A | -Decreased ROS levels | [44] |
-Decreased apoptotic signalling | ||||||
TNTs | Primary rat astrocytes | Primary rat astrocytes and neurons | H2O2 or serum depletion | N/A | [45] | |
TNTs | primary mouse neurons | primary mouse astrocytes | 5xFAD | N/A | -Increased transmitophagy | [33] |
TNTs | Glioblastoma stem-like cells | Glioblastoma stem-like cells | Irradiation | C1: no effect | N/A | [36] |
C2: increased transfer |
4. Effects of Mitochondrial Transfer in the Brain
- To enhance cell viability via transferring healthy mitochondria to stressed/injured cells;
- To enhance degradation of dysfunctional mitochondria via transferring unhealthy mitochondria to healthy cells;
- To modulate glia-mediated neuroinflammation.
4.1. Enhancement of Cell Viability
4.2. Enhancement of Mitochondrial Degradation
4.3. Modulation of Glia-Mediated Neuroinflammation
4.4. Deleterious Effects
5. Mitochondrial Transfer in Brain Injury and Disease
5.1. Brain Injury
5.2. Neurodegenerative Diseases
5.3. Neurodevelopmental Disease
5.4. Chemotherapy
6. Therapeutic Strategies Targeting Mitochondrial Transfer
6.1. Pharmacologic Approaches
6.1.1. CD38
6.1.2. MIRO-1
6.1.3. CX43
6.1.4. Mitochondrial Fission/Fusion
6.2. Mitochondrial Transplantation
Disease Model | Source of Mitochondria | Method of Delivery for AMT | Effects | References |
---|---|---|---|---|
Stroke | MMSC with overexpressed Miro-1 | I.V. injection | -Increased neurological function | [49] |
-MCAO model of focal ischemia | ||||
Stroke | Primary mouse astrocytes | Local injection into peri-infarct cortex | -Upregulation of cell survival signals | [20] |
-Focal cerebral ischaemia | ||||
Stroke | Baby hamster kidney fibroblast (BHK-21) | ICV or systemic intra-arterial injection | -Increased motor performance | [78] |
-MCAO model of focal ischemia | -Decreased brain infarct area | |||
-Decreased neuronal death | ||||
Stroke | Mouse placenta | I.V. injection | -Decreased brain infarct area | [79] |
-Focal cerebral ischaemia | ||||
Stroke | Primary mouse astrocytes | I.V. injection | -Increased neuronal viability | [80] |
-Intracerebral haemorrhage | -Reduced neurologic deficits | |||
-Restored Mn-SOD levels | ||||
Stroke | Human umbilical-cord-derived mesenchymal stem cells | ICV | -Decreased apoptosis | [81] |
-MCAO model of focal ischemia | -Decreased gliosis | |||
-Improved motor function | ||||
-Decreased brain infarct area | ||||
Chemotherapy-induced neurotoxicity | MSC | Intranasal | -Reduced apoptosis | [50] |
-Cisplatin treatment | ||||
Alzheimer’s disease | HeLa cells | I.V. injection | -Improved cognitive function | [85] |
-Amyloid-β intracerebroventricularly injected | -Decreased neuronal loss | |||
-Decreased gliosis | ||||
-Increased citrate-synthase and cytochrome c oxidase activities | ||||
Parkinson’s disease | PC12 cells | Local injection into MFB | -Improved locomotive activity | [86] |
-6-OHDA-lesioned rat model | or | -Increased neuronal survival | ||
Human osteosarcoma cybrids | -Restored mitochondrial dynamics | |||
Parkinson’s disease | Rat liver | Intranasal | -Improved locomotive activity | [87] |
-6-OHDA-lesioned rat model | -Increased neuronal survival | |||
-Decreased oxidative damage | ||||
Parkinson’s disease | HepG2 cells | I.V. injection | -Improved locomotive activity | [88] |
-MPTP-induced mouse model | -Increased ATP levels | |||
-Decreased ROS levels | ||||
Multiple sclerosis | Neural stem cells | ICV | -Ameliorated EAE severity | [56] |
-MOG35-55-induced EAE | ||||
Schizophrenia | Human lymphoblasts | Intra-prefrontal cortex injection | -Rescued attentional deficits | [96] |
-Prenatal poly-I:C exposure | Or | -Increased MMP | ||
Rat brain | ||||
Traumatic brain injury | Mouse liver | Local injection into cerebral cortex | -Increased ATP levels | [84] |
-Controlled cortical impact | Mouse muscle | -Upregulated astrocytic BDNF | ||
Improved spatial memory and cognitive function | ||||
Traumatic brain injury | Mouse brain | Local injection into cerebral cortex | -Decreased apoptosis | [83] |
Controlled cortical impact | -Increased angiogenesis | |||
-Decreased brain oedema | ||||
-Decreased blood brain barrier leakage |
7. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Fairley, L.H.; Grimm, A.; Eckert, A. Mitochondria Transfer in Brain Injury and Disease. Cells 2022, 11, 3603. https://doi.org/10.3390/cells11223603
Fairley LH, Grimm A, Eckert A. Mitochondria Transfer in Brain Injury and Disease. Cells. 2022; 11(22):3603. https://doi.org/10.3390/cells11223603
Chicago/Turabian StyleFairley, Lauren H., Amandine Grimm, and Anne Eckert. 2022. "Mitochondria Transfer in Brain Injury and Disease" Cells 11, no. 22: 3603. https://doi.org/10.3390/cells11223603