Characterization of mitochondrial calpain-5

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Medicine

Background:

• Calpain-5 is a Ca2+-dependent cysteine protease involved in cellular processes like apoptosis.
• Mutations in calpain-5 are linked to neovascular inflammatory vitreoretinopathy.
• Mitochondrial and cytosolic calpain-5 functions require further investigation.

Purpose of the Study:

• To characterize mitochondrial calpain-5 in porcine retinas, human HeLa cells, and mice.
• To investigate the activation mechanisms of mitochondrial calpain-5 under different conditions.

Main Methods:

• Subcellular fractionation was used to isolate mitochondria.
• Experiments were conducted on porcine retinas, HeLa cells, and C57BL/6J mice.
• Endoplasmic reticulum (ER) stress was induced using thapsigargin.

Main Results:

• Mitochondrial calpain-5 underwent proteolysis/autolysis at low Ca2+ concentrations in porcine retinas.
• ER stress induced by thapsigargin led to mitochondrial calpain-5 activation in HeLa cells.
• Mitochondrial calpain-5, unlike its cytosolic counterpart, activated during early ER stress in mice.

Conclusions:

• Mitochondrial calpain-5 is activated by low Ca2+ in vitro and by ER stress in vivo.
• A novel mitochondrial calpain system responsive to early ER stress has been identified.
• Targeting mitochondrial calpain-5 activation may offer therapeutic strategies for ER stress-related disorders.