TY - JOUR
T1 - Leishmania donovani
T2 - Intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells
AU - Sen, Nilkantha
AU - Das, Benu Brata
AU - Ganguly, Agneyo
AU - Banerjee, Bijoylaxhmi
AU - Sen, Tanusree
AU - Majumder, Hemanta K.
N1 - Funding Information:
We thank Prof. S. Roy, the Director of our institute, for his interest in this work. We also acknowledge Dr. Gayatri Tripathi and Mr. Sailen Dey for their help with confocal microscopy and electron microscopy. N.S is supported by Senior Research Fellowship from the Council for Scientific and Industrial Research; Government of India.
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Apoptosis-like death
KW - Dyskinetoplastidy
KW - Leishmania
KW - Luteolin
KW - Mitochondria
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U2 - 10.1016/j.exppara.2006.03.013
DO - 10.1016/j.exppara.2006.03.013
M3 - Article
C2 - 16707127
AN - SCOPUS:33750027629
SN - 0014-4894
VL - 114
SP - 204
EP - 214
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 3
ER -