Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria
Abstract
:1. Introduction
2. Mitochondria Move along Microtubules and Actin Filaments
2.1. Microtubules
2.2. Actin
3. Molecular Motors Transport Mitochondria via Microtubules
4. Mitochondrial Docking and Anchoring Machineries in Neurons
5. Metabolic Control of Mitochondrial Transport
5.1. Calcium
5.2. Glucose
5.3. ATP
5.4. Hypoxia
5.5. Reactive Oxygen Species (ROS)
5.6. Growth Factors and Neurotransmitters
6. Mitophagy
7. Specialized Cytoskeleton Structures Allow Mitochondria to Cross Cell Boundaries
7.1. Structure of TNTs
7.2. Transfer of Mitochondria to Neuronal Cells
7.3. The Heterogeneous Nature of TNTs
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACRT10 | Actin-related protein 10 |
ADP | Adenosine diphosphate |
AMP | Adenosine monophosphate |
AMPK | AMP-activated protein kinase |
APC | Adenomatous polyposis coli |
ATP | Adenosine triphosphate |
CLASP2 | Cytoplasmic linker-associated protein 2 |
DHC | Dynein heavy chain |
DIC | Dynein intermediate chain |
DLC | Dynein light chain |
DLIC | Dynein light intermediate chain |
FEZ1 | Fasciculation and elongation protein zeta 1 |
FHL2 | Four and a half LIM domain protein 2 |
FRZ | Frizzled |
GDP | Guanosine diphosphate |
GSK3β | Glycogen synthase kinase 3β |
GTP | Guanosine triphosphate |
HDAC6 | Histone deacetylate 6 |
HIF-1α | Hypoxia-inducible factor 1α |
HUMMR | Hypoxia up-regulated mitochondrial movement regulator |
JNK | c-Jun N-terminal Kinase |
KHC | Kinesin heavy chain |
KLC | Kinesin light chain |
KLP6 | Kinesin-Like Protein 6 |
LRP | Low-density lipoprotein receptor-related protein |
MAP | Microtubule-associated protein |
MAP1B | Micro+A1:B48tubule-associated protein 1B |
MAPK | Mitogen-activated protein kinase |
MCAO | Middle cerebral artery occlusion |
MCU | Mitochondrial calcium uniporter |
MFN2 | Mitofusin 2 |
MiST | Mitochondrial shape transition |
MSC | Mesenchymal stem cell |
mtDNA | Mitochondrial DNA |
MTX | Metaxins |
MYO | Myosin |
NGF | Nerve growth factor |
NO | Nitric oxide |
OMM | Outer mitochondrial membrane |
PI3K | Phosphoinositide 3-kinase |
PTM | Post-translational modification |
RANBP2 | Ran-binding protein 2 |
ROBO | Roundabout |
SNPH | Syntaphilin |
STORM | Stochastic optical reconstruction microscopy |
SYBU | Syntabulin |
TNT | Tunneling nanotube |
TRAK | Trafficking kinesin protein |
VDAC | Voltage-dependent anion-selective channel |
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Disease | Treatment | Clinical Outcome | Ref. |
---|---|---|---|
Rat model of Parkinson’s disease | Mitochondria | Restored mitochondrial functions and reduced oxidative damage in dopaminergic neurons | [127] |
Mouse model of PD | Mitochondria | Increased electron transport chain activity, reduced ROS level and prevented apoptosis and necrosis | [128] |
Rat model of schizophrenia | Mitochondria | Prevented mitochondrial dysfunction in intra-prefrontal cortex neurons and emergence of attention deficit | [129] |
Middle cerebral artery occlusion (MCAO) in rats | Mitochondria | Decreased brain infarct volume and reversed neurological deficits. | [130] |
MCAO in rats | Mesenchymal multipotent stromal cells | Reduced infarct volume in the brain and partial restoration of neurological status * | [131] |
Ischemic stress in rats | Mitochondria | Restored motor performance, attenuated brain infarct area and neuronal cell death | [132] |
MCAO in rats | MSC-derived mitochondria | Declined blood creatine phosphokinase level, abolished apoptosis, decreased astroglyosis and microglia activation, reduced infarct size and improved motor function | [133] |
Ischemia–reperfusion stroke injury | MSCs | Rescued damaged cerebrovascular system in stroke | [123] |
Spinal cord injury in rats | Mitochondria | Maintenance of normal bioenergetics without recovery of motor and sensory functions | [134] |
Traumatic brain injury in rats | MSC-derived mitochondria | Improved sensorimotor functions | [135] |
Nerve crush injury in rats | Mitochondria | Improved neurobehaviors, electrophysiology of nerve conduction and muscle activities | [136] |
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Zaninello, M.; Bean, C. Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria. Biomolecules 2023, 13, 938. https://doi.org/10.3390/biom13060938
Zaninello M, Bean C. Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria. Biomolecules. 2023; 13(6):938. https://doi.org/10.3390/biom13060938
Chicago/Turabian StyleZaninello, Marta, and Camilla Bean. 2023. "Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria" Biomolecules 13, no. 6: 938. https://doi.org/10.3390/biom13060938