S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3
2010 (English)In: Cell Research, ISSN 1001-0602, E-ISSN 1748-7838, Vol. 20, no 3, 314-331 p.Article in journal (Refereed) Published
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H+-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, ΔTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either ΔTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
Place, publisher, year, edition, pages
2010. Vol. 20, no 3, 314-331 p.
S100A8/A9, Calprotectin, lysosomal activation, mitochondrial membrane potential, BNIP3, Beclin-1
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:liu:diva-86904DOI: 10.1038/cr.2009.129ISI: 000275816300008PubMedID: 19935772OAI: oai:DiVA.org:liu-86904DiVA: diva2:583053