{"id":4679,"date":"2026-03-27T02:26:47","date_gmt":"2026-03-27T02:26:47","guid":{"rendered":"https:\/\/globalnewstoday.uk\/index.php\/2026\/03\/27\/reversal-of-atp-synthase-is-a-key-attribute-accompanying-cellular-differentiation-of-trypanosoma-brucei-insect-forms-nature\/"},"modified":"2026-03-27T02:26:47","modified_gmt":"2026-03-27T02:26:47","slug":"reversal-of-atp-synthase-is-a-key-attribute-accompanying-cellular-differentiation-of-trypanosoma-brucei-insect-forms-nature","status":"publish","type":"post","link":"https:\/\/globalnewstoday.uk\/index.php\/2026\/03\/27\/reversal-of-atp-synthase-is-a-key-attribute-accompanying-cellular-differentiation-of-trypanosoma-brucei-insect-forms-nature\/","title":{"rendered":"Reversal of ATP synthase is a key attribute accompanying cellular differentiation of Trypanosoma brucei insect forms – Nature"},"content":{"rendered":"

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Communications Biology<\/i><\/a> , Article\u00a0number:\u00a0<\/span> (2026<\/span>) Cite this article<\/a>
<\/use><\/svg> We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
The mitochondrial Fo<\/sub>F1<\/sub>-ATP synthase is a reversible nanomachine that normally produces ATP via oxidative phosphorylation but under stress conditions it can reverse to maintain the mitochondrial membrane potential at the expense of ATP, a process regulated by the conserved inhibitory factor 1 (IF1). We show that ATP synthase reversal also occurs during in vitro-induced differentiation of the unicellular parasite Trypanosoma brucei<\/i>, partially mirroring events in the tsetse fly. Differentiation of insect forms is marked by increased expression of alternative oxidase and reduced levels of trypanosomal IF1 (TbIF1), changes that may promote ATP synthase reversal. Parasites lacking TbIF1 efficiently progressed to the mammalian-infective form, coinciding with increased ATP synthase reversal, a higher ADP\/ATP ratio, elevated phosphorylation of AMP-activated protein kinase (AMPK), enhanced proline-supported respiration, and increased mitochondrial and cellular reactive oxygen species (ROS). In contrast, inducible TbIF1 overexpression diminished these hallmarks and locked parasites in the initial insect stage. Our findings reveal that TbIF1 downregulation enables life cycle progression and underscore a regulatory role for the ATP synthase\u2013IF1 axis.
All data supporting the findings of this study, including the uncropped and unprocessed Western blot images (Supplementary Fig.\u00a04<\/a>), are available within the paper. The source data for all charts\/graphs, description of T. brucei<\/i> strains, and list of used oligonucleotides can be found in Supplementary Data\u00a01<\/a>. All other data are available from the corresponding author on reasonable request.
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We would like to thank Martina Slapni\u010dkov\u00e1 for excellent technical support and Prof. Christos Chinopoulos (Semmelweis University, Budapest) for stimulating discussions. We would also like to express our gratitude to the Biology Centre core facilities, namely to the Laboratory of Electron Microscopy, to the Laboratory of Microscopy and Histology, and to the Laboratory of Analytical Biochemistry and Metabolomics. This work was supported by the Horizon Europe ERC MitoSignal project no. 101044951, OP JAK CZ.02.01.01\/00\/22_008\/0004575 RNA for therapy, Co-Funded by the European Union and by Czech Science Foundation project no.23-07370S to AZ. We acknowledge the BC CAS core facility LEM supported by the Czech-BioImaging large RI project (LM2023050 and OP VVV CZ.02.1.01\/0.0\/0.0\/18_046\/0016045 funded by MEYS CR) for their support with obtaining scientific data presented in this paper.
Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic
Michaela Kunzov\u00e1,\u00a0Eva Dole\u017eelov\u00e1,\u00a0Brian Panicucci\u00a0&\u00a0Alena Z\u00edkov\u00e1
Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic
Michaela Kunzov\u00e1\u00a0&\u00a0Alena Z\u00edkov\u00e1
Institute of Entomology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic
Martin Moos
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M.K. and E.D. performed the experiments and analyzed the data. M.M. performed the mass spectrometry analyses. B.P. contributed to methodology design. A.Z. conceived and supervised the study and acquired funding. A.Z. wrote the first draft of the manuscript, and M.K. and E.D. contributed to subsequent versions and revisions. All authors reviewed and approved the final manuscript.
Correspondence to Alena Z\u00edkov\u00e1<\/a>.
The authors declare no competing interests.
Communications Biology<\/i> thanks Michael Boshart and the other anonymous reviewer(s) for their contribution to the peer review of this work. Primary Handling Editors: Nishith Gupta and David Favero. A peer review file is available.
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Kunzov\u00e1, M., Dole\u017eelov\u00e1, E., Moos, M. et al.<\/i> Reversal of ATP synthase is a key attribute accompanying cellular differentiation of Trypanosoma brucei<\/i> insect forms. Commun Biol<\/i> (2026). https:\/\/doi.org\/10.1038\/s42003-026-09933-z
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