Heart mitochondria and calpain 1: Location, function, and targets

• Mitochondrial calpain 1 (mit-CPN1) is present in both intermembrane space and matrix.
• Activation of the mit-CPN1 within the intermembrane pace cleaves apoptosis inducing factor (AIF).
• Activation of the mit-CPN1 within the matrix impairs metabolism and favors permeability transition.
• Prevention of mit-CPN1 activation is a potential strategy to decrease cardiac injury during ischemia–reperfusion.

Calpain 1 is an ubiquitous Ca2 +-dependent cysteine protease. Although calpain 1 has been found in cardiac mitochondria, the exact location within mitochondrial compartments and its function remain unclear. The aim of the current review is to discuss the localization of calpain 1 in different mitochondrial compartments in relationship to its function, especially in pathophysiological conditions. Briefly, mitochondrial calpain 1 (mit-CPN1) is located within the intermembrane space and mitochondrial matrix. Activation of the mit-CPN1 within intermembrane space cleaves apoptosis inducing factor (AIF), whereas the activated mit-CPN1 within matrix cleaves complex I subunits and metabolic enzymes. Inhibition of the mit-CPN1 could be a potential strategy to decrease cardiac injury during ischemia–reperfusion.