Granzyme a, a stealth killer in the mitochondrion.
The induction of caspase-independent cell death by killer lymphocytes involves the serine protease granzyme A (GzmA). In this issue, Martinvalet et al. (2008) show that GzmA penetrates the mitochondrial matrix without perturbing normal mitochondrial functions. In the mitochondrial matrix, GzmA cleaves NDUFS3 (a component of the electron transport chain) leading to production of reactive oxygen species and ultimately to cell death.
Lucken-Ardjomande
Safa
S
Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, Geneva CH-1211, Switzerland.
Martinou
Jean-Claude
JC
D000818:Animals; D016923:Cell Death; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology
D017382:Reactive Oxygen Species; D009245:NADH Dehydrogenase; D053804:Granzymes; C472512:NDUFS3 protein, human