A new tool to determine the cellular metabolic landscape: nanotechnology to the study of Friedreich's ataxia.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
17 12 2019
Historique:
received: 06 10 2019
accepted: 12 11 2019
entrez: 19 12 2019
pubmed: 19 12 2019
medline: 6 11 2020
Statut: epublish

Résumé

Understanding the cell response to oxidative stress in disease is an important but difficult task. Here, we demonstrate the feasibility of using a nanomotion sensor to study the cellular metabolic landscape. This nanosensor permits the non-invasive real-time detection at the single-cell level and offers high sensitivity and time resolution. We optimised the technique to study the effects of frataxin overexpression in a cellular model of Friedreich's ataxia, a neurodegenerative disease caused by partial silencing of the FXN gene. Previous studies had demonstrated that FXN overexpression are as toxic as silencing, thus indicating the importance of a tight regulation of the frataxin levels. We probed the effects of frataxin overexpression in the presence of oxidative stress insults and measured the metabolic response by the nanosensor. We show that the nanosensor provides new detailed information on the metabolic state of the cell as a function of time, that agrees with and complements data obtained by more traditional techniques. We propose that the nanosensor can be used in the future as a new and powerful tool to study directly how drugs modulate the effects of oxidative stress on Friedreich's ataxia patients and, more in general, on other neurodegenerative processes.

Identifiants

pubmed: 31848436
doi: 10.1038/s41598-019-55799-z
pii: 10.1038/s41598-019-55799-z
pmc: PMC6917756
doi:

Substances chimiques

Iron-Binding Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

19282

Subventions

Organisme : Medical Research Council
ID : U117584256
Pays : United Kingdom

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Auteurs

Tommaso Vannocci (T)

UK Dementia Research Institute at King's College London, London, SE5 9RT, United Kingdom.
The Wohl Institute at King's College London, London, SE5 9RT, United Kingdom.

Simone Dinarelli (S)

Istituto di Struttura della Materia - CNR, Via del Fosso del Cavaliere 100, 00133, Rome, Italy.

Marco Girasole (M)

Istituto di Struttura della Materia - CNR, Via del Fosso del Cavaliere 100, 00133, Rome, Italy.

Annalisa Pastore (A)

UK Dementia Research Institute at King's College London, London, SE5 9RT, United Kingdom. annalisa.pastore@crick.ac.uk.
The Wohl Institute at King's College London, London, SE5 9RT, United Kingdom. annalisa.pastore@crick.ac.uk.

Giovanni Longo (G)

Istituto di Struttura della Materia - CNR, Via del Fosso del Cavaliere 100, 00133, Rome, Italy. longo@ism.cnr.it.

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Classifications MeSH