Research3d ago0 views

Suppression of mitochondrial energy production by a photosynthetic bacterial cupredoxin peptide inhibits tumor growth.

Peptide research just scored another win. A team from the University of Illinois and collaborators in Italy have engineered a new peptide, aurB, derived from a photosynthetic bacterial cupredoxin. The target: mitochondrial energy production in cancer cells. The result: measurable inhibition of tumor growth and metastasis.

Signal Transduct Target Ther

by Naffouje SA, Tran DB, Rademacher DJ et al.

“Suppression of mitochondrial energy production by a photosynthetic bacterial cupredoxin peptide inhibits tumor growth. Naffouje SA(#)(1)(2), Tran DB(#)(1), Rademacher DJ(3), Botti V(4), Christov K(1), Green A(1), Li W(5), Phong NHT(1), Cannistraro S(4), Bizzarri AR(4), Das Gupta TK(1), Yamada T(6)(7). Author information: (1)Department of Surgery, Division of Surgical Oncology, University of Illinois College of Medicine, Chicago, IL, USA. (2)General Surgery, Cleveland Clinic, Cleveland, OH, USA. (3)Department of Microbiology and Immunology and Core Microscopy Facility, Loyola University Chicago, Chicago, IL, USA. (4)Biophysics and Nanoscience Centre, Department of Ecology and Biology, Università della Tuscia, Viterbo, Italy. (5)Richard & Loan Hill Department of Bioengineering, University of Illinois, College of Engineering, Chicago, IL, USA. (6)Department of Surgery, Division of Surgical Oncology, University of Illinois College of Medicine, Chicago, IL, USA. tohru@uic.edu. (7)Richard & Loan Hill Department of Bioengineering, University of Illinois, College of Engineering, Chicago, IL, USA. tohru@uic.edu. (#)Contributed equally Accumulating evidence shows that bacteria influence cancer homeostasis, yet the effects of tumor‑associated microbes and their products remain largely unexplored. We previously reported that P. aeruginosa-cancer crosstalk suppresses tumors via the bacterial cupredoxin azurin, and we developed an azurin‑derived peptide that was tested in clinical trials. Building on our previous studies, we studied tumor-resident bacteria for novel therapeutics and targets. Photosynthetic bacteria from the phylum Chloroflexota, including a member of the class Chloroflexia, identified in tumors, carry the cupredoxin auracyanin gene. Based on the structural and chemical characteristics of auracyanin, we designed a novel cell-penetrating peptide, aurB. Plant chloroplasts are thought to have evolved from a bacterial endosymbiont, and both chloroplasts and mitochondria possess shared proteins essential for ATP-dependent energy production, indicating that these bacterial-derived proteins may influence mitochondrial function. Consistent with this model, we demonstrated that aurB, a peptide from cupredoxin auracyanin B, localized at mitochondria, blocked energy production by targeting ATP synthase in prostate cancer cells, thereby significantly inhibiting tumor growth. More strikingly, combination treatment with aurB and radiation therapy significantly inhibited tumor growth in a tibial bone metastasis model. Moreover, the number of metastatic lesions in the lungs was also significantly lower upon aurB treatment. Multiplex RNA-expression profiling revealed that the inhibition of ATP production by aurB increased the efficacy of radiation therapy by modulating multiple pathways involving HIF-1α. Our findings indicate that electron transfer proteins could represent an important source of promising novel peptide-based agents that target the aberrantly activated mitochondrial energy system in cancer. © 2026. The Author(s). Conflict of interest statement: Competing interests: The authors declare no competing interests.”

Here's what happened. The researchers looked at bacteria living in tumors and found that some, like Chloroflexia, carry a cupredoxin called auracyanin. Inspired by this, they built aurB—a cell-penetrating peptide that homes in on mitochondria. Once inside prostate cancer cells, aurB goes straight for ATP synthase, the enzyme responsible for energy production. When ATP drops, cancer cells struggle to grow.

Key takeaway: Peptides like aurB can directly disrupt cancer metabolism at the mitochondrial level.

This isn't just theory. In a tibial bone metastasis model, aurB alone slowed tumor growth. Combined with radiation, the effect was even stronger. Lung metastases also dropped. RNA profiling showed aurB modulates key pathways, including HIF-1α, enhancing the impact of radiation.

•

Peptide aurB targets mitochondria, blocks ATP synthase

•

Tumor and metastasis growth drop with aurB treatment

•

Combining aurB with radiation therapy boosts results

•

Modulates cellular pathways tied to cancer metabolism

This work highlights a new class of research peptides sourced from bacterial electron transfer proteins. The field is moving fast, and the potential for novel peptide-based strategies looks wide open.

Want to keep up with new findings like this? Check out the peptide research index for more breakthroughs and research compounds. For sourcing or purchasing, visit our vendor directory.

Peptide science is just getting started—expect more smart ideas like aurB in the pipeline.

Back to News Read original on Signal Transduct Target Ther

Suppression of mitochondrial energy production by a photosynthetic bacterial cupredoxin peptide inhibits tumor growth.

Related Reading

Eu(3+)-mediated dual-crosslinked collagen-mimetic peptide/sodium alginate hydrogel for 3D-printed skin wound dressings.

Antimicrobial-potentiated colorectal cancer therapy with synchronized tumoricidal immunity via a self-deliverable nanopeptide.

Real-world weight impact upon tirzepatide discontinuation at a single-center endocrinology clinic in patients with overweight or obesity.