Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F21%3A43904224" target="_blank" >RIV/60076658:12310/21:43904224 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60077344:_____/21:00554949

Výsledek na webu

<a href="https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202001579RR" target="_blank" >https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202001579RR</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fj.202001579RR" target="_blank" >10.1096/fj.202001579RR</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms

Popis výsledku v původním jazyce

The mitochondrial inner membrane glycerophospholipid cardiolipin (CL) associates with mitochondrial proteins to regulate their activities and facilitate protein complex and supercomplex formation. Loss of CL leads to destabilized respiratory complexes and mitochondrial dysfunction. The role of CL in an organism lacking a conventional electron transport chain (ETC) has not been elucidated. Trypanosoma brucei bloodstream forms use an unconventional ETC composed of glycerol-3-phosphate dehydrogenase and alternative oxidase (AOX), while the mitochondrial membrane potential (Delta psi m) is generated by the hydrolytic action of the FoF1-ATP synthase (aka FoF1-ATPase). We now report that the inducible depletion of cardiolipin synthase (TbCls) is essential for survival of T brucei bloodstream forms. Loss of CL caused a rapid drop in ATP levels and a decline in the Delta psi m. Unbiased proteomic analyses revealed a reduction in the levels of many mitochondrial proteins, most notably of FoF1-ATPase subunits and AOX, resulting in a strong decline of glycerol-3-phosphate-stimulated oxygen consumption. The changes in cellular respiration preceded the observed decrease in FoF1-ATPase stability, suggesting that the AOX-mediated ETC is the first pathway responding to the decline in CL. Select proteins and pathways involved in glucose and amino acid metabolism were upregulated to counteract the CL depletion-induced drop in cellular ATP.

Název v anglickém jazyce

Depletion of cardiolipin induces major changes in energy metabolism in Trypanosoma brucei bloodstream forms

Popis výsledku anglicky

The mitochondrial inner membrane glycerophospholipid cardiolipin (CL) associates with mitochondrial proteins to regulate their activities and facilitate protein complex and supercomplex formation. Loss of CL leads to destabilized respiratory complexes and mitochondrial dysfunction. The role of CL in an organism lacking a conventional electron transport chain (ETC) has not been elucidated. Trypanosoma brucei bloodstream forms use an unconventional ETC composed of glycerol-3-phosphate dehydrogenase and alternative oxidase (AOX), while the mitochondrial membrane potential (Delta psi m) is generated by the hydrolytic action of the FoF1-ATP synthase (aka FoF1-ATPase). We now report that the inducible depletion of cardiolipin synthase (TbCls) is essential for survival of T brucei bloodstream forms. Loss of CL caused a rapid drop in ATP levels and a decline in the Delta psi m. Unbiased proteomic analyses revealed a reduction in the levels of many mitochondrial proteins, most notably of FoF1-ATPase subunits and AOX, resulting in a strong decline of glycerol-3-phosphate-stimulated oxygen consumption. The changes in cellular respiration preceded the observed decrease in FoF1-ATPase stability, suggesting that the AOX-mediated ETC is the first pathway responding to the decline in CL. Select proteins and pathways involved in glucose and amino acid metabolism were upregulated to counteract the CL depletion-induced drop in cellular ATP.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular 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

2021

Kód důvěrnosti údajů

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

Název periodika

FASEB Journal

ISSN

0892-6638

e-ISSN

—

Svazek periodika

35

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

—

Kód UT WoS článku

000590888700001

EID výsledku v databázi Scopus

2-s2.0-85096656101