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Published on: January 22, 2017
USP30 impairs mitochondrial quality control and aggravates oxidative damage after traumatic brain injury
Yang Wu1, Qing Hu2, Hongbo Cheng3
1Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi province, 710038, China; Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei province, 050000, China.
Abstract:
Clinical progress in the treatment of traumatic brain injury (TBI) is hindered by the poor understanding of the molecular mechanisms that underlie secondary brain injury (SBI). USP30, a mitochondrial deubiquitinase, has been implicated in the pathological progress of various diseases. However, the precise role of USP30 in TBI-induced SBI remains unclear. In this study, we found that USP30 was differentially upregulated after TBI in humans and mice. Immunofluorescence staining further revealed that the enhanced USP30 mainly localized in neurons. Neuron-specific knockout of USP30 reduced lesion volumes, mitigated brain edema, and attenuated neurological deficits after TBI in mice. Additionally, we found that USP30 deficiency effectively suppressed oxidative stress and neuronal apoptosis in TBI. Those protective effects of USP30 loss may be attributed, at least partially, to the reduction of TBI-induced impairment of mitochondrial quality control, including mitochondrial dynamics, function, and mitophagy. Collectively, our findings identify a previously undisclosed role of USP30 in the pathophysiology of TBI and lay a preliminary foundation for future research in this field.
Insights
USP30, a mitochondrial enzyme, is upregulated after traumatic brain injury (TBI). Inhibiting USP30 in neurons reduces brain damage and improves outcomes by enhancing mitochondrial health after TBI.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathophysiology
Background:
- Traumatic brain injury (TBI) clinical progress is limited by understanding secondary brain injury (SBI) molecular mechanisms.
- USP30, a mitochondrial deubiquitinase, is linked to various diseases, but its role in TBI-induced SBI is unknown.
Purpose of the Study:
- To investigate the role of USP30 in TBI-induced secondary brain injury.
- To determine the effects of USP30 inhibition on neuronal survival and mitochondrial function post-TBI.
Main Methods:
- Analysis of USP30 expression in human and mouse TBI models.
- Neuron-specific knockout of USP30 in mice subjected to TBI.
- Assessment of lesion volume, brain edema, neurological deficits, oxidative stress, and apoptosis.
- Evaluation of mitochondrial dynamics, function, and mitophagy.
Main Results:
- USP30 was upregulated in neurons following TBI in humans and mice.
- Neuron-specific USP30 knockout reduced lesion volume, brain edema, and neurological deficits.
- USP30 deficiency suppressed oxidative stress and neuronal apoptosis.
- Loss of USP30 improved mitochondrial quality control, including dynamics, function, and mitophagy.
Conclusions:
- USP30 plays a significant role in the pathophysiology of TBI-induced SBI.
- Targeting USP30 may offer a therapeutic strategy for mitigating TBI consequences.
- Further research is warranted to elucidate USP30's precise mechanisms in TBI.
