Protective role of vitamin B6 against mitochondria damage in Drosophila models of SCA3

Nan, Yuyu; Lin, Jingjing; Cui, Ying; Yao, Jinpeng; Yang, Yufeng; Li, Qinghua

doi:10.1016/j.neuint.2021.104979

Cited by 15 publications

(10 citation statements)

References 42 publications

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“…Proteome analyses of an SCA3 knockin mouse model demonstrated energy metabolism and dysfunctional expression of mitochondrial proteins as an early event in the pathogenesis [ 22 ]. Therapeutically, vitamin B6 supplementation in an SCA3 Drosophila model resulted in mitochondrial protection of polyQ-induced cellular toxicity [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination

Harmuth

Weber

Zimmer

et al. 2022

IJMS

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Dysfunctional mitochondria are linked to several neurodegenerative diseases. Metabolic defects, a symptom which can result from dysfunctional mitochondria, are also present in spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, the most frequent, dominantly inherited neurodegenerative ataxia worldwide. Mitochondrial dysfunction has been reported for several neurodegenerative disorders and ataxin-3 is known to deubiquitinylate parkin, a key protein required for canonical mitophagy. In this study, we analyzed mitochondrial function and mitophagy in a patient-derived SCA3 cell model. Human fibroblast lines isolated from SCA3 patients were immortalized and characterized. SCA3 patient fibroblasts revealed circular, ring-shaped mitochondria and featured reduced OXPHOS complexes, ATP production and cell viability. We show that wildtype ataxin-3 deubiquitinates VDAC1 (voltage-dependent anion channel 1), a member of the mitochondrial permeability transition pore and a parkin substrate. In SCA3 patients, VDAC1 deubiquitination and parkin recruitment to the depolarized mitochondria is inhibited. Increased p62-linked mitophagy, autophagosome formation and autophagy is observed under disease conditions, which is in line with mitochondrial fission. SCA3 fibroblast lines demonstrated a mitochondrial phenotype and dysregulation of parkin-VDAC1-mediated mitophagy, thereby promoting mitochondrial quality control via alternative pathways.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination

Harmuth

Weber

Zimmer

et al. 2022

IJMS

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“…Results are in concordance with the previous literature reports stating that Yfh1p deficiency gives rise to imbalances in iron and copper homeostasis (Han et al, 2017). The other enriched term, “vitamin B6 biosynthetic process,” may be due to the protective effect of vitamin B6 against mitochondrial damage (Nan et al, 2021): mutant cells accumulate damaged mitochondria (Wilson & Roof, 1997) and to cope up with this phenomenon, they may upregulate vitamin B6 biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

Insights from yeast: Transcriptional reprogramming following metformin treatment is similar to that of deferiprone in a yeast Friedreich's ataxia model

Börklü

2023

Yeast

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In the absence of YFH1, the yeast ortholog of the human FXN gene, budding yeast Saccharomyces cerevisiae experience similar problems to those of cells with Friedreich's ataxia (FRDA). The comparable phenotypic traits consist of impaired respiration, problems in iron homeostasis, decreased oxidative stress tolerance, and diminished iron–sulfur cluster synthesis, rendering yeast of potential use in FRDA modeling and drug trials. Deferiprone, an iron chelator, is one of the long‐term studied potential drugs for FRDA, whereas metformin is a biguanide prescribed to treat type 2 diabetes. In the present study, the effects of deferiprone and metformin treatment on the yeast FRDA model are explored via RNA‐sequencing analyses. The comparative inquiry of transcriptome data reveals new promising roles for metformin in FRDA treatment since deferiprone and metformin treatments produce overlapping transcriptional and phenotypic responses in YFH1Δ cells. The results revealed that both deferiprone and metformin treatment does not rescue aerobic respiration in YFH1Δ cells, but they alleviate the FRDA phenotype probably by triggering the retrograde mitochondria‐to‐nucleus signaling.

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“…Second, Su(var)3-9 and HP1a, which contribute to maintaining heterochromatin stability, protect ECs [45]. In addition, the non-stop identity complex, histones H3 and H4, and vitamin B6 protect differentiated ECs and promote survival [49][50][51]. A recent report suggested that the epigenomic effects of VitD are mediated by epigenetic factors such as IncRNAs, miRNAs, methylation, acetylation, and the interactions between VDR and certain genes such as SLC30A10 [52].…”

Section: Discussionmentioning

confidence: 99%

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut

Park,

Na,

Kim

2024

Aging

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Adult stem cells are pivotal for maintaining tissue homeostasis, and their functional decline is linked to aging and its associated diseases, influenced by the niche cells' environment. Age-and cancer-related reduction of vitamin D and its receptor levels are well documented in human clinical studies. However, the mechanisms through which the vitamin D/vitamin D receptor pathway contributes to anti-aging and extends life expectancy are not well understood. In this study, we aimed to determine the protective role of the vitamin D/vitamin D receptor pathway in differentiated enterocytes (ECs) during intestinal stem cell (ISC) aging. By utilizing a wellestablished Drosophila midgut model for stem cell aging biology, we revealed that vitamin D receptor knockdown in ECs induced ISC proliferation, EC death, ISC aging, and enteroendocrine cell differentiation. Additionally, age-and oxidative stress-induced increases in ISC proliferation and centrosome amplification were reduced by vitamin D treatment. Our findings suggest a direct evidence of the anti-aging role of the vitamin D/vitamin D receptor pathway and provides insights into the molecular mechanisms underlying healthy aging in Drosophila.

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Protective role of vitamin B6 against mitochondria damage in Drosophila models of SCA3

Cited by 15 publications

References 42 publications

Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination

Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination

Insights from yeast: Transcriptional reprogramming following metformin treatment is similar to that of deferiprone in a yeast Friedreich's ataxia model

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut

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