Intracellular serpins, firewalls and tissue necrosis.
Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.
Marciniak
Stefan J
SJ
Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.
Lomas
David A
DA
D000799:Angioedema / Q000201:enzymology; D004646:Emphysema / Q000201:enzymology; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology / Q000473:pathology; D008958:Models, Molecular; D009154:Mutation; D009336:Necrosis / Q000201:enzymology*; D019636:Neurodegenerative Diseases / Q000201:enzymology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015843:Serpins / Q000145:classification / Q000235:genetics / Q000502:physiology; D013927:Thrombosis / Q000201:enzymology*
D015843:Serpins