Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F20%3A00533119" target="_blank" >RIV/86652036:_____/20:00533119 - isvavai.cz</a>

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s12640-020-00285-y" target="_blank" >https://link.springer.com/article/10.1007/s12640-020-00285-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12640-020-00285-y" target="_blank" >10.1007/s12640-020-00285-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes

Popis výsledku v původním jazyce

The interaction of alpha-synuclein with mitochondria in both typical and atypical Parkinson's disease is a critical component of degeneration. The mechanism of cell-to-cell propagation of pathological alpha-synuclein in synucleinopathies is unclear. Intercellular exchange of mitochondria along tunnelling nanotubes has been described in other diseases, such as cancer, however, its role in synucleinopathies is unknown. Pathological alpha-synuclein species have been demonstrated previously to move from cell to cell via tunnelling nanotubes. This process was further explored using co-culture and monoculture systems to determine if alpha-synuclein binds to migrating mitochondria within tunnelling nanotubes. Super-resolution analysis via stimulated emission depletion microscopy showed interaction between alpha-synuclein with the mitochondrial outer membrane and the presence of alpha-synuclein associated with mitochondria in tunnelling nanotubes between 1321N1, differentiated THP-1 and SH-SY5Y cell types. siRNA knockdown of Miro1, a critical protein-bridging mitochondria to the motor adaptor complex, had no effect on mitochondrial density or alpha-synuclein association with mitochondria in tunnelling nanotubes. The results show that alpha-synuclein aggregates associate with mitochondria in intercellular tunnelling nanotubes, suggesting that mitochondria-mediated alpha-synuclein transfer between cells may contribute to cell-to-cell spread of alpha-synuclein aggregates and disease propagation.

Název v anglickém jazyce

Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes

Popis výsledku anglicky

The interaction of alpha-synuclein with mitochondria in both typical and atypical Parkinson's disease is a critical component of degeneration. The mechanism of cell-to-cell propagation of pathological alpha-synuclein in synucleinopathies is unclear. Intercellular exchange of mitochondria along tunnelling nanotubes has been described in other diseases, such as cancer, however, its role in synucleinopathies is unknown. Pathological alpha-synuclein species have been demonstrated previously to move from cell to cell via tunnelling nanotubes. This process was further explored using co-culture and monoculture systems to determine if alpha-synuclein binds to migrating mitochondria within tunnelling nanotubes. Super-resolution analysis via stimulated emission depletion microscopy showed interaction between alpha-synuclein with the mitochondrial outer membrane and the presence of alpha-synuclein associated with mitochondria in tunnelling nanotubes between 1321N1, differentiated THP-1 and SH-SY5Y cell types. siRNA knockdown of Miro1, a critical protein-bridging mitochondria to the motor adaptor complex, had no effect on mitochondrial density or alpha-synuclein association with mitochondria in tunnelling nanotubes. The results show that alpha-synuclein aggregates associate with mitochondria in intercellular tunnelling nanotubes, suggesting that mitochondria-mediated alpha-synuclein transfer between cells may contribute to cell-to-cell spread of alpha-synuclein aggregates and disease propagation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neurotoxicity Research

ISSN

1029-8428

e-ISSN

—

Svazek periodika

SEP 2020

Číslo periodika v rámci svazku

SEP 2020

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

—

Kód UT WoS článku

000569293100002

EID výsledku v databázi Scopus

2-s2.0-85091009949