Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression

S. Oh, S. Jo, M. Bajzikova, HS. Kim, TTP. Dao, J. Rohlena, JM. Kim, J. Neuzil, S. Park

. 2023 ; 13 (2) : 438-457. [pub] 20230101

Language English Country Australia

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

Persistent link   https://www.medvik.cz/link/bmc23004705

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 (ρ0) cancer cells with lower proliferation rates to clarify the undefined roles of mitochondria in cancer growth. Methods and results: Despite extensive metabolic downregulation, ρ0 cells exhibited high glycerol-3-phosphate (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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23004705
003      
CZ-PrNML
005      
20230425171654.0
007      
ta
008      
230418s2023 at f 000 0|eng||
009      
AR
024    7_
$a 10.7150/thno.75973 $2 doi
035    __
$a (PubMed)36632231
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a at
100    1_
$a Oh, Sehyun $u College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea
245    10
$a Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression / $c S. Oh, S. Jo, M. Bajzikova, HS. Kim, TTP. Dao, J. Rohlena, JM. Kim, J. Neuzil, S. Park
520    9_
$a 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 (ρ0) cancer cells with lower proliferation rates to clarify the undefined roles of mitochondria in cancer growth. Methods and results: Despite extensive metabolic downregulation, ρ0 cells exhibited high glycerol-3-phosphate (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.
650    _2
$a energetický metabolismus $7 D004734
650    _2
$a ethery $x metabolismus $7 D004987
650    12
$a glycerolfosfátdehydrogenasa $x genetika $x metabolismus $7 D005993
650    12
$a mitochondrie $x enzymologie $7 D008928
650    12
$a protoonkogenní proteiny c-akt $x metabolismus $7 D051057
650    _2
$a zvířata $7 D000818
650    _2
$a myši $7 D051379
650    12
$a nádory $x enzymologie $x patologie $7 D009369
650    _2
$a lidé $7 D006801
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Jo, Sihyang $u College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea
700    1_
$a Bajzikova, Martina $u School of Pharmacy and Medical Science, Griffith University, Southport, Qld, Australia
700    1_
$a Kim, Han Sun $u College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea
700    1_
$a Dao, Thien T P $u College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea
700    1_
$a Rohlena, Jakub $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Kim, Jin-Mo $u College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea
700    1_
$a Neuzil, Jiri $u School of Pharmacy and Medical Science, Griffith University, Southport, Qld, Australia $u Institute of Biotechnology, Czech Academy of Sciences, Prague-West, Czech Republic $u Faculty of Science, Charles University, Prague, Czech Republic
700    1_
$a Park, Sunghyouk $u College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea
773    0_
$w MED00177173 $t Theranostics $x 1838-7640 $g Roč. 13, č. 2 (2023), s. 438-457
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36632231 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230418 $b ABA008
991    __
$a 20230425171650 $b ABA008
999    __
$a ok $b bmc $g 1925035 $s 1190914
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 13 $c 2 $d 438-457 $e 20230101 $i 1838-7640 $m Theranostics $n Theranostics $x MED00177173
LZP    __
$a Pubmed-20230418

Find record

Citation metrics

Archiving options