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The calcium dependent cysteine protease μ‐calpain is located in the mitochondrial intermembrane space
Author(s) -
Garcia Matthew,
Badugu Rama Krishna,
Bondada Vimala,
Joshi Aashish,
Geddes James W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1017.3
Subject(s) - calpain , intermembrane space , mitochondrial intermembrane space , microbiology and biotechnology , calpastatin , mitochondrion , cysteine protease , chemistry , biology , biochemistry , proteases , enzyme , gene , escherichia coli , bacterial outer membrane
The ubiquitous proteases, m‐ and μ‐calpain, are thought to be localized in the cytosolic compartment, as is their endogenous inhibitor calpastatin. As a result, it is unclear how calpains become activated. We previously demonstrated that μ‐calpain was found enriched in mitochondrial fractions isolated from rat cerebral cortex and SH‐SY5Y neuroblastoma cells (Garcia, et. al. 2005. BBRC 338, 1241–1247), but the submitochondrial localization of μ‐calpain was not determined. In this study, we localized the large catalytic calpain 1 subunit along with the regulatory calpain small subunit 1, which together form μ‐calpain, to the mitochondrial intermembrane space. The results further demonstrate that calpain 1 is imported into mitochondria and contains a mitochondrial targeting sequence in its NH2‐terminus. This targeting sequence is not present in the large subunit of m‐calpain, which is not imported into mitochondria. The localization of μ‐calpain to the mitochondrial intermembrane space is consistent with a role for μ‐calpain in the cleavage of intermembrane space proteins including apoptosis inducing factor, providing a potential mechanism of mitochondrial μ‐calpain activation contributing to caspase independent cell death. This work was supported by the NIH, USPHS grants; P01NS058484, P01AG010836, R01NS045726, T32DA022738 and by the Kentucky Spinal Cord and Head Injury Research Trust.