Leishmania requires Rab7-mediated degradation of endocytosed hemoglobin for their growth
Open accessAbstract
Leishmania is unable to synthesize heme and must acquire it from exogenous source, the mechanism of which is not known. We have shown that Leishmania endocytoses hemoglobin (Hb) and subsequently degrade it probably to generate heme. To understand how internalized Hb is degraded, we have cloned and expressed Rab7 homolog from Leishmania donovani. Interestingly, Rab7 in Leishmania is found to be localized both on early and late endocytic compartment and regulates both uptake and degradation of endocytosed Hb demonstrating that Rab7 in Leishmania play a very unique role connecting both early and late events of Hb endocytosis. Our data also indicate that overexpression of Rab7:WT in Leishmania induces transport of Hb to lysosomes and rapidly degrade internalized Hb. Whereas Hb transport to lysosomes and its degradation is significantly inhibited in cells overexpressing Rab7:T21N, a GDP locked mutant of Rab7. Moreover, cells overexpressing Rab7:T21N grow at a slower rate (<50%) compared with control Leishmania. Addition of exogenous hemin recovers the growth of Rab7:T21N mutant cells almost to the control level, suggesting that intracellular heme generated by Rab7-mediated Hb degradation is required for optimal growth of the parasites. Thus, our results identify a potential target which might be exploited to suppress the growth of Leishmania.
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Leishmania species are unable to synthesize heme by themselves and express receptors for the uptake of HB or heme.
“In contrast to P. falciparum, Leishmania species, which can cause skin, mucocutaneous or systemic infections, are unable to synthesize heme by themselves and thus express receptors for the uptake of HB or heme, respectively (Krishnamurthy et al., 2005;Patel et al., 2008).”
From Iron in infection and immunity (2020) · cites this paper as Patel et al., 2008
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Liang, P., He, L., Yu, J., Xie, Z., Chen, X., Mao, Q., Liang, C., Huang, Y., Lu, G., & Yu, X. (2015) · Parasitology Research · doi:10.1007/s00436-015-4372-8
Lingfu, K., & Bao-liang, B. (2011) · Journal of Animal and Veterinary Advances · doi:10.3923/javaa.2011.585.592
Unconventional role of Rab4 in the secretory pathway in Leishmania
Ansari, I., Singh, A. K., Kapoor, A., & Mukhopadhyay, A. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119687
Self-citationGurjar, D., Saha, B., Pai, K., Sundar, S., Ponte-Sucre, A., Bodhale, N., & Saha, B. (2026) · Parasitology International · doi:10.1016/j.parint.2026.103267
Analysis of structure and stability of Leishmania donovani Rab5a and Rab5b
Pandey, D., Zohib, M., Chaurasia, A., Ansari, H., Chowdhury, A., Pal, R. K., Tripathi, S., Jain, A., Biswal, B. K., Siddiqi, M. I., et al. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.152349
- Authors
- Patel, N., Singh, S. B., Basu, S. K., & Mukhopadhyay, A.
- Affiliations
- National Institute of Immunology (IN)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-03-11
- Volume
- 105
- Issue
- 10
- Pages
- 3980-3985
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2268841
- OpenAlex
- W2109837906
- Cited by
- 56
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 4 · 2013: 4 · 2012: 2
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indo-French Centre for the Promotion of Advanced Research
- National Institute of Immunology
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Keywords
- Leishmania donovani, Rab7, heme acquisition, lysosomal degradation, parasite growth, antiparasitic drug targets
- MeSH terms
- rab7 GTP-Binding Proteins, Amino Acid Sequence, Animals, Cell Compartmentation, Cloning, Molecular, Endocytosis, Hemoglobins, Leishmania donovani, Lysosomes, Molecular Sequence Data, Protein Processing, Post-Translational, Sequence Alignment, Sequence Homology, Amino Acid, rab GTP-Binding Proteins, Protein Transport, Mutant Proteins
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