Suramin exposure alters cellular metabolism and mitochondrial energy production in African trypanosomes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F20%3A43901446" target="_blank" >RIV/60076658:12310/20:43901446 - isvavai.cz</a>

Alternative codes found

RIV/60077344:_____/20:00540776

Result on the web

<a href="https://www.jbc.org/lens/jbc/295/24/8331" target="_blank" >https://www.jbc.org/lens/jbc/295/24/8331</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA120.012355" target="_blank" >10.1074/jbc.RA120.012355</a>

Result language

angličtina

Original language name

Suramin exposure alters cellular metabolism and mitochondrial energy production in African trypanosomes

Original language description

Introduced about a century ago, suramin remains a frontline drug for the management of early-stage East African trypanosomiasis (sleeping sickness). Cellular entry into the causative agent, the protozoan parasiteTrypanosoma brucei, occurs through receptor-mediated endocytosis involving the parasite&apos;s invariant surface glycoprotein 75 (ISG75), followed by transport into the cytosol via a lysosomal transporter. The molecular basis of the trypanocidal activity of suramin remains unclear, but some evidence suggests broad, but specific, impacts on trypanosome metabolism (i.e.polypharmacology). Here we observed that suramin is rapidly accumulated in trypanosome cells proportionally to ISG75 abundance. Although we found little evidence that suramin disrupts glycolytic or glycosomal pathways, we noted increased mitochondrial ATP production, but a net decrease in cellular ATP levels. Metabolomics highlighted additional impacts on mitochondrial metabolism, including partial Krebs&apos; cycle activation and significant accumulation of pyruvate, corroborated by increased expression of mitochondrial enzymes and transporters. Significantly, the vast majority of suramin-induced proteins were normally more abundant in the insect forms compared with the blood stage of the parasite, including several proteins associated with differentiation. We conclude that suramin has multiple and complex effects on trypanosomes, but unexpectedly partially activates mitochondrial ATP-generating activity. We propose that despite apparent compensatory mechanisms in drug-challenged cells, the suramin-induced collapse of cellular ATP ultimately leads to trypanosome cell death.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

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

Publication year

2020

Confidentiality

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

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Volume of the periodical

295

Issue of the periodical within the volume

24

Country of publishing house

US - UNITED STATES

Number of pages

17

Pages from-to

8331-8347

UT code for WoS article

000542965700019

EID of the result in the Scopus database

2-s2.0-85086496610