Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F23%3A00572138" target="_blank" >RIV/86652036:_____/23:00572138 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/23:10476701
Result on the web
<a href="https://www.thno.org/v13p0438.htm" target="_blank" >https://www.thno.org/v13p0438.htm</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.7150/thno.75973" target="_blank" >10.7150/thno.75973</a>
Alternative languages
Result language
angličtina
Original language name
Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression
Original language description
Rationale: Despite growing evidence for mitochondria's involvement in cancer, the roles of specific metabolic components outside the respiratory complex have been little explored. We conducted metabolomic studies on mitochondrial DNA (mtDNA)-deficient (rho 0) cancer cells with lower proliferation rates to clarify the undefined roles of mitochondria in cancer growth.Methods and results: Despite extensive metabolic downregulation, rho 0 cells exhibited high glycerol-3phosphate (G3P) level, due to low activity of mitochondrial glycerol-3-phosphate dehydrogenase (GPD2). Knockout (KO) of GPD2 resulted in cell growth suppression as well as inhibition of tumor progression in vivo. Surprisingly, this was unrelated to the conventional bioenergetic function of GPD2. Instead, multi-omics results suggested major changes in ether lipid metabolism, for which GPD2 provides dihydroxyacetone phosphate (DHAP) in ether lipid biosynthesis. GPD2 KO cells exhibited significantly lower ether lipid level, and their slower growth was rescued by supplementation of a DHAP precursor or ether lipids. Mechanistically, ether lipid metabolism was associated with Akt pathway, and the downregulation of Akt/mTORC1 pathway due to GPD2 KO was rescued by DHAP supplementation.Conclusion: Overall, the GPD2-ether lipid-Akt axis is newly described for the control of cancer growth. DHAP supply, a non-bioenergetic process, may constitute an important role of mitochondria in cancer.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10601 - Cell biology
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
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Theranostics
ISSN
1838-7640
e-ISSN
1838-7640
Volume of the periodical
13
Issue of the periodical within the volume
2
Country of publishing house
AU - AUSTRALIA
Number of pages
20
Pages from-to
438-457
UT code for WoS article
000977797700001
EID of the result in the Scopus database
2-s2.0-85144217830