Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11310/23:10476701

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Theranostics

ISSN

1838-7640

e-ISSN

1838-7640

Svazek periodika

13

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

AU - Austrálie

Počet stran výsledku

20

Strana od-do

438-457

Kód UT WoS článku

000977797700001

EID výsledku v databázi Scopus

2-s2.0-85144217830