Depleting chemoresponsive mitochondrial fission mediator DRP1 does not mitigate sarcoma resistance
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00081781" target="_blank" >RIV/00159816:_____/24:00081781 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/25:00140743
Result on the web
<a href="https://www.life-science-alliance.org/content/8/2/e202402870#ack-1" target="_blank" >https://www.life-science-alliance.org/content/8/2/e202402870#ack-1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.26508/lsa.202402870" target="_blank" >10.26508/lsa.202402870</a>
Alternative languages
Result language
angličtina
Original language name
Depleting chemoresponsive mitochondrial fission mediator DRP1 does not mitigate sarcoma resistance
Original language description
Specific patterns of mitochondrial dynamics have been repeatedly reported to promote drug resistance in cancer. However, whether targeting mitochondrial fission- and fusion-related proteins could be leveraged to combat multidrug-resistant pediatric sarcomas is poorly understood. Here, we demonstrated that the expression and activation of the mitochondrial fission mediator DRP1 are affected by chemotherapy exposure in common pediatric sarcomas, namely, rhabdomyosarcoma and osteosarcoma. Unexpectedly, decreasing DRP1 activity through stable DRP1 knockdown neither attenuated sarcoma drug resistance nor affected growth rate or mitochondrial network morphology. The minimal impact on sarcoma cell physiology, along with the up-regulation of fission adaptor proteins (MFF and FIS1) detected in rhabdomyosarcoma cells, suggests an alternative DRP1-independent mitochondrial fission mechanism that may efficiently compensate for the lack of DRP1 activity. By exploring the upstream mitophagy and mitochondrial fission regulator, AMPK alpha 1, we found that markedly reduced AMPK alpha 1 levels are sufficient to maintain AMPK signaling capacity without affecting chemosensitivity. Collectively, our findings challenge the direct involvement of DRP1 in pediatric sarcoma drug resistance and highlight the complexity of yet-to-be-characterized noncanonical regulators of mitochondrial dynamics.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10600 - Biological sciences
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Life Science Alliance
ISSN
2575-1077
e-ISSN
2575-1077
Volume of the periodical
8
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
"e202402870"
UT code for WoS article
001372057300001
EID of the result in the Scopus database
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