Axonal transport dysfunction of mitochondria in traumatic brain injury: A novel therapeutic target

Shin, Samuel S.; Karlsson, Michael; Mazandi, Vanessa; Ranganathan, Abhay; Hallowell, Thomas; Delso, Nile; Kilbaugh, Todd J.

doi:10.1016/j.expneurol.2020.113311

Cited by 9 publications

(8 citation statements)

References 90 publications

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“… 12 , 23–25 Synaptic mitochondria are synthesized in the cell body of neurons and then trafficked down the axon or dendrite to the pre- and post-synaptic terminals, respectively. 19 , 25–28 Mitochondrial transport is disrupted after TBI, which likely contributes to neuronal dysfunction after injury (reviewed by Shin and colleagues 29 ). Mitochondria within the synapse are continuously exposed to Ca 2+ because of the large influxes involved in synaptic transmission, making these mitochondrial fractions more sensitive to Ca 2+ overload than non-synaptic mitochondria, even in uninjured conditions.…”

Section: Introductionmentioning

confidence: 99%

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice

Kalimon,

Vekaria,

Velmurugan

et al. 2023

Neurotrauma Reports

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Traumatic brain injury (TBI) is caused by an impact or penetrating injury to the head resulting in abnormal brain function. Mitochondrial dysfunction is an important hallmark of TBI and has been thoroughly studied in male rodent models of brain injury, but relatively little is known about these outcomes in females. These studies were designed to examine sex as a biological variable for mitochondria-related outcomes after the severe controlled cortical impact (CCI) mouse model of TBI. Synaptic and non-synaptic mitochondria were isolated from the sham- or CCI-injured cortex as well as the hippocampus ipsilateral to the craniotomy 3, 12, 24, or 48 h post-surgery, and then bioenergetics were measured. Subtle variations were observed in the timeline of mitochondrial dysfunction between sexes. Non-synaptic cortical mitochondria from injured females showed early impairment at 12 h post-CCI compared to mitochondria from injured males at 24 h post-CCI. Contrastingly, in the synaptic fraction, mitochondria from injured males showed early impairment at 12 h post-CCI, whereas mitochondria from injured females showed impairment at 24 h post-CCI. Based on bioenergetic impairments at 24 h post-CCI, synaptic and non-synaptic mitochondrial calcium loading was also measured at this time point. Consistent with bioenergetic data at 24 h, non-synaptic mitochondria from injured males had increased calcium loading compared to uninjured control, but this effect was not observed in females. Finally, histological assessment of cortical tissue sparing in each sex was measured at 7 days post-injury. There was a lack of sex-based differences in cortical tissue sparing after severe CCI. Overall, there were some subtle sex differences in mitochondrial outcomes after CCI, but these findings were not statistically significant. This study highlights the importance of utilizing both sexes when measuring mitochondrial function after severe CCI.

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Section: Introductionmentioning

confidence: 99%

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice

Kalimon,

Vekaria,

Velmurugan

et al. 2023

Neurotrauma Reports

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“…Indeed, selective removal of harmful components from mitochondria has been reported, such as resident proteases in mitochondria ( Misgeld and Schwarz, 2017 ). Defective proteins can also fuse with lysosomes through small vesicles sprouting from mitochondria, known as mitochondria-derived vesicles (MDVs) ( Shin et al, 2020 ). The above mechanisms improve the precision, efficiency, and flexibility of mitochondrial quality control in neurons.…”

Section: Local Disposition Of Mitochondriamentioning

confidence: 99%

“…Fusion is initiated by Mfn1/2-regulated fusion of the OMM, followed by OPA1-regulated fusion of the inner mitochondrial membrane (IMM) ( Filadi et al, 2018 ). Fusion allows the exchange of mitochondrial proteins and mitochondrial DNA (mtDNA), which reduces metabolic stress and is one of the pathways to repair damaged mitochondria ( Youle and van der Bliek, 2012 ; Shin et al, 2020 ). Mitochondrial fission and fusion have been covered in detail in several fascinating reviews and are, therefore, beyond the scope of this review ( Burté et al, 2015 ; Dorn, 2019 ; Sprenger and Langer, 2019 ; Valdinocci et al, 2019 ; Fernandes et al, 2020 ; Shin et al, 2020 ; Adebayo et al, 2021 ; Yang et al, 2021 ; López-Doménech and Kittler, 2023 ).…”

Section: Mitochondrial Fusion-fission Dynamicsmentioning

confidence: 99%

“…The role of microtubule disruption on mitochondrial translocation will be discussed in the next section rather than here. Mitochondrial dynamics, including the extent of fusion, fission, and translocation, is altered following TBI, which has been well summarized by Shin et al (2020) . A recent study reported the role of Miro1 in TBI rats ( Chen et al, 2021 ).…”

Section: Evidence For the Involvement Of Mitochondrial Transport In A...mentioning

confidence: 99%

“…Fusion allows the exchange of mitochondrial proteins and mitochondrial DNA (mtDNA), which reduces metabolic stress and is one of the pathways to repair damaged mitochondria (Youle and van der Bliek, 2012;Shin et al, 2020). Mitochondrial fission and fusion have been covered in detail in several fascinating reviews and are, therefore, beyond the scope of this review (Burté et al, 2015;Dorn, 2019;Sprenger and Langer, 2019;Valdinocci et al, 2019;Fernandes et al, 2020;Shin et al, 2020;Adebayo et al, 2021;Yang et al, 2021;López-Doménech and Kittler, 2023). Mitochondrial motility has been reported to be a determinant of fusion (Twig et al, 2010).…”

Section: Mitochondrial Fusion-fission Dynamicsmentioning

confidence: 99%

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Mitochondrial transport in neurons and evidence for its involvement in acute neurological disorders

Lu,

Feng,

Liu

et al. 2023

Front. Neurosci.

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Ensuring mitochondrial quality is essential for maintaining neuronal homeostasis, and mitochondrial transport plays a vital role in mitochondrial quality control. In this review, we first provide an overview of neuronal mitochondrial transport, followed by a detailed description of the various motors and adaptors associated with the anterograde and retrograde transport of mitochondria. Subsequently, we review the modest evidence involving mitochondrial transport mechanisms that has surfaced in acute neurological disorders, including traumatic brain injury, spinal cord injury, spontaneous intracerebral hemorrhage, and ischemic stroke. An in-depth study of this area will help deepen our understanding of the mechanisms underlying the development of various acute neurological disorders and ultimately improve therapeutic options.

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Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases

et al. 2022

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Axonal transport dysfunction of mitochondria in traumatic brain injury: A novel therapeutic target

Cited by 9 publications

References 90 publications

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice

Mitochondrial transport in neurons and evidence for its involvement in acute neurological disorders

Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases

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