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Mitochondrial abnormalities in induced pluripotent stem cells-derived motor neurons from patients with riboflavin transporter deficiency
- Source :
- Antioxidants, Vol 9, Iss 1252, p 1252 (2020), Antioxidants, Volume 9, Issue 12
- Publication Year :
- 2020
-
Abstract
- Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by sensorineural deafness and motor neuron degeneration. Since riboflavin plays key functions in biological oxidation-reduction reactions, energy metabolism pathways involving flavoproteins are affected in RTD. We recently generated induced pluripotent stem cell (iPSC) lines from affected individuals as an in vitro model of the disease and documented mitochondrial impairment in these cells, dramatically impacting cell redox status. This work extends our study to motor neurons (MNs), i.e., the cell type most affected in patients with RTD. Altered intracellular distribution of mitochondria was detected by confocal microscopic analysis (following immunofluorescence for superoxide dismutase 2 (SOD2), as a dual mitochondrial and antioxidant marker), and &beta<br />III-Tubulin, as a neuronal marker. We demonstrate significantly lower SOD2 levels in RTD MNs, as compared to their healthy counterparts. Mitochondrial ultrastructural abnormalities were also assessed by focused ion beam/scanning electron microscopy. Moreover, we investigated the effects of combination treatment using riboflavin and N-acetylcysteine, which is a widely employed antioxidant. Overall, our findings further support the potential of patient-specific RTD models and provide evidence of mitochondrial alterations in RTD-related iPSC-derived MNs&mdash<br />emphasizing oxidative stress involvement in this rare disease. We also provide new clues for possible therapeutic strategies aimed at correcting mitochondrial defects, based on the use of antioxidants.
- Subjects :
- 0301 basic medicine
Cell type
Motor neuron
Physiology
Clinical Biochemistry
SOD2
Mitochondrion
Riboflavin transporter deficiency
medicine.disease_cause
Biochemistry
Article
Superoxide dismutase
03 medical and health sciences
0302 clinical medicine
energy metabolism
medicine
Electron microscopy
oxidative stress
motor neurons
Neurodegeneration
Induced pluripotent stem cell
Molecular Biology
riboflavin transporter deficiency
electron microscopy
biology
Chemistry
lcsh:RM1-950
neurodegeneration
Cell Biology
Energy metabolism
medicine.disease
Cell biology
Mitochondria
mitochondria
antioxidants
lcsh:Therapeutics. Pharmacology
030104 developmental biology
biology.protein
Oxidative stre
Antioxidant
030217 neurology & neurosurgery
Intracellular
Oxidative stress
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Antioxidants, Vol 9, Iss 1252, p 1252 (2020), Antioxidants, Volume 9, Issue 12
- Accession number :
- edsair.doi.dedup.....5b78f98931ea9c8b124e45b6a3eaf2cd