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Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major
Author(s) -
Zalila Habib,
González Iveth J.,
ElFadili Amal Kuendig,
Delgado Maria Belen,
Desponds Chantal,
Schaff Cédric,
Fasel Nicolas
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07443.x
Subject(s) - biology , leishmania , caspase , microbiology and biotechnology , cytoplasm , mitochondrion , programmed cell death , cysteine protease , cysteine , biochemistry , leishmania major , kinetoplastida , protozoa , apoptosis , enzyme , parasite hosting , immunology , protozoal disease , world wide web , computer science , malaria
Summary Metacaspases are cysteine peptidases that could play a role similar to caspases in the cell death programme of plants, fungi and protozoa. The human protozoan parasite Leishmania major expresses a single metacaspase (LmjMCA) harbouring a central domain with the catalytic dyad histidine and cysteine as found in caspases. In this study, we investigated the processing sites important for the maturation of LmjMCA catalytic domain, the cellular localization of LmjMCA polypeptides, and the functional role of the catalytic domain in the cell death pathway of Leishmania parasites. Although LmjMCA polypeptide precursor form harbours a functional mitochondrial localization signal (MLS), we determined that LmjMCA polypeptides are mainly localized in the cytoplasm. In stress conditions, LmjMCA precursor forms were extensively processed into soluble forms containing the catalytic domain. This domain was sufficient to enhance sensitivity of parasites to hydrogen peroxide by impairing the mitochondrion. These data provide experimental evidences of the importance of LmjMCA processing into an active catalytic domain and of its role in disrupting mitochondria, which could be relevant in the design of new drugs to fight leishmaniasis and likely other protozoan parasitic diseases.