Mitochondrial localization of mu-calpain.
Calcium-dependent cysteine proteases, calpains, have physiological roles in cell motility and differentiation but also play a pathological role following insult or disease. The ubiquitous calpains are widely considered to be cytosolic enzymes, although there has been speculation of a mitochondrial calpain. Within a highly enriched fraction of mitochondria obtained from rat cortex and SH-SY5Y human neuroblastoma cells, immunoblotting demonstrated enrichment of the 80kDa mu-calpain large subunit and 28kDa small subunit. In rat cortex, antibodies against domains II and III of the large mu-calpain subunit also detected a 40kDa fragment, similar to the autolytic fragment generated following incubation of human erythrocyte mu-calpain with Ca(2+). Mitochondrial proteins including apoptosis inducing factor and mitochondrial Bax are calpain substrates, but the mechanism by which calpains gain access to these proteins is uncertain. Mitochondrial localization of mu-calpain places the enzyme in proximity to its mitochondrial substrates and to Ca(2+) released from mitochondrial stores.
Garcia
Matthew
M
Spinal Cord and Brain Injury Research Center and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
Bondada
Vimala
V
Geddes
James W
JW
D000818:Animals; D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002154:Calpain; C449002:mu-calpain