Evidence for mitochondrial control of neuronal polarity

Mattson, Mark P.; Partin, James

doi:10.1002/(sici)1097-4547(19990401)56:1<8::aid-jnr2>3.3.co;2-7

Cited by 16 publications

(23 citation statements)

References 50 publications

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“…Mitochondria play important roles in neuronal developmental processes, including the establishment of axon polarity and the regulation of neurite outgrowth (36,37). Since it has been reported that Vpr influences mitochondrial function in several cell types and induces mitochondrial membrane depolarization (5,25,26), Vpr also may induce mitochondrial dysfunction in neuronal progenitor cells.…”

Section: Inhibitionmentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Vpr Inhibits Axonal Outgrowth through Induction of Mitochondrial Dysfunction

Kitayama

Miura

Ando

et al. 2008

J Virol

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Human immunodeficiency virus type 1 (HIV-1)-infected macrophages damage mature neurons in the brain, although their effect on neuronal development has not been clarified. In this study, we show that HIV-1-infected macrophages produce factors that impair the development of neuronal precursor cells and that soluble viral protein R (Vpr) is one of the factors that has the ability to suppress axonal growth. Cell biological analysis revealed that extracellularly administered recombinant Vpr (rVpr) clearly accumulated in mitochondria where a Vpr-binding protein adenine nucleotide translocator localizes and also decreased the mitochondrial membrane potential, which led to ATP synthesis. The depletion of ATP synthesis reduced the transportation of mitochondria within neurites. This mitochondrial dysfunction inhibited axonal growth even when the frequency of apoptosis was not significant. We also found that point mutations of arginine (R) residues to alanine (A) residues at positions 73, 77, and 80 rendered rVpr incapable of causing mitochondrial membrane depolarization and axonal growth inhibition. Moreover, the Vpr-induced inhibition was suppressed after treatment with a ubiquinone analogue (ubiquinone-10). Our results suggest that soluble Vpr is a major viral factor that causes a disturbance in neuronal development through the induction of mitochondrial dysfunction. Since ubiquinone-10 protects the neuronal plasticity in vitro, it may be a therapeutic agent that can offer defense against HIV-1-associated neurological disease.

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Section: Inhibitionmentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Vpr Inhibits Axonal Outgrowth through Induction of Mitochondrial Dysfunction

Kitayama

Miura

Ando

et al. 2008

J Virol

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“…Impaired Neuronal Outgrowth in NPC1Ϫ/Ϫ Neurons Is Restored by ATP Treatment in Culture-Because ATP is required for the development of neurons (32), the effect of NPC1 deficiency on neurite outgrowth was investigated using neurons prepared from cerebral cortices derived from NPC1ϩ/ϩ, NPC1ϩ/Ϫ, and NPC1Ϫ/Ϫ mouse brains. Using immunocytochemistry, the staining neurons for ␤-tubulin indicated that while neurite extension was clearly evident at 72 h in NPC1ϩ/ϩ and NPC1ϩ/Ϫ neurons, it was impaired in NPC1Ϫ/Ϫ neurons (Fig.…”

Section: The Level Of Cholesterol and Phospholipids In Cellular Fractmentioning

confidence: 99%

Altered Cholesterol Metabolism in Niemann-Pick Type C1 Mouse Brains Affects Mitochondrial Function

Gong

et al. 2005

Journal of Biological Chemistry

186

183

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Niemann-Pick type C1 (NPC1) disease is a fatal hereditary disorder characterized by a defect in cholesterol trafficking and progressive neurodegeneration. Although the NPC1 gene has been identified, the molecular mechanism responsible for neuronal dysfunction in brains of patients with NPC1 disease remains unknown. This study demonstrates that the amount of cholesterol within mitochondria membranes is significantly elevated in NPC1 mouse brains and neural cells. In addition, the mitochondrial membrane potential, the activity of ATP synthase, and henceforth the level of ATP are markedly decreased in NPC1 mouse brains and neurons. Importantly, reducing the level of cholesterol within mitochondrial membranes using methyl-␤-cyclodextrin can restore the activity of ATP synthase. Finally, NPC1 neurons show an impaired neurite outgrowth, which can be rescued by exogenous ATP. These results suggest that mitochondrial dysfunctions and subsequent ATP deficiency, which are induced by altered cholesterol metabolism in mitochondria, may be responsible for neuronal impairment in NPC1 disease.

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“…During the development, neuronal stem cells proliferate and differentiate into neurons; subsequently axons and dendrites form synapses [134][135]. The role of mitochondria in neuroplasticity is illustrated in Figure 3 [20].…”

Section: Mitochondria and Neuroplasticitymentioning

confidence: 99%

“…Nerve growth factor (NGF) was found as one of the signals inducing accumulation of mitochondria in the active growing cone [136]. Interestingly, when the ATP production is impaired and cells provide alternative source of energy, axogenesis is abolished although growth of dendrites remains relatively unaffected [134].…”

Section: Mitochondria and Neuroplasticitymentioning

confidence: 99%