Leishmania donovani: Intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells

Nilkantha Sen, Benu Brata Das, Agneyo Ganguly, Bijoylaxhmi Banerjee, Tanusree Sen, Hemanta K. Majumder

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Leishmaniasis presents a spectrum of diseases ranging from benign cutaneous lesions to the often-fatal visceralizing form. Luteolin, a dietary flavone induces apoptosis-like death in both promastigote and amastigote forms of Leishmania, the causative agent of the diseases. Here, we have elucidated the mechanism of action of luteolin by analyzing the mitochondrial and cytosolic changes associated with apoptosis-like death of leishmanial cells. In Leishmania donovani, treatment with luteolin induces the loss of both maxicircles and minicircles which resulted in the formation of dyskinetoplastid cells. The loss of mitochondrial DNA causes reduction in the activities of complex I, II, III, and IV of electron transport chain. However, the mitochondrial ATPase activity of complex V remains almost unaltered during treatment with luteolin but the sensitivity to oligomycin is lost. The inactivation of ETC complex is associated with decrease in mitochondrial as well as glycolytic ATP production, which is responsible for depolarization of Δψm and alteration in mitochondrial structure. This event is followed by the release of cytochrome c from mitochondria in mt-DNA depleted leishmanial cells and causes an activation of caspase like proteases. Collectively our results provide the first insight into the mechanistic pathway of apoptosis-like death where inhibition of glycolytic ATP production is an essential event responsible for depolarization of Δψm in mt-DNA depleted cells to propagate apoptosis-like death in leishmanial cells.

Original languageEnglish (US)
Pages (from-to)204-214
Number of pages11
JournalExperimental Parasitology
Volume114
Issue number3
DOIs
StatePublished - Nov 1 2006

Fingerprint

Luteolin
Leishmania donovani
Adenosine Triphosphate
Apoptosis
flavone
Oligomycins
Leishmaniasis
Leishmania
DNA
Caspases
Electron Transport
Cytochromes c
Mitochondrial DNA
Adenosine Triphosphatases
Mitochondria
Peptide Hydrolases
Cell Death
Skin

Keywords

  • Apoptosis-like death
  • Dyskinetoplastidy
  • Leishmania
  • Luteolin
  • Mitochondria

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

Cite this

Leishmania donovani : Intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells. / Sen, Nilkantha; Das, Benu Brata; Ganguly, Agneyo; Banerjee, Bijoylaxhmi; Sen, Tanusree; Majumder, Hemanta K.

In: Experimental Parasitology, Vol. 114, No. 3, 01.11.2006, p. 204-214.

Research output: Contribution to journalArticle

Sen, Nilkantha ; Das, Benu Brata ; Ganguly, Agneyo ; Banerjee, Bijoylaxhmi ; Sen, Tanusree ; Majumder, Hemanta K. / Leishmania donovani : Intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells. In: Experimental Parasitology. 2006 ; Vol. 114, No. 3. pp. 204-214.
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