Lee, Ho-June Pyo, Jong-Ok Oh, Yumin Kim, Hyo-Jin Hong, Se-Hoon Jeon, Young-Jun Kim, Hyunjoo Cho, Dong-Hyung Woo, Ha-Na Song, Sungmin Nam, Jung-Hyun Kim, Hyo Joon Kim, Key-Sun Jung, Yong-Keun 2024-01-21T00:05:54Z 2024-01-21T00:05:54Z 2021-08-31 2007-11 1465-7392 https://pubs.kist.re.kr/handle/201004/134018 Mitochondrial proteins function as essential regulators in apoptosis. Here, we show that mitochondrial adenylate kinase 2 ( AK2) mediates mitochondrial apoptosis through the formation of an AK2-FADD-caspase-10 (AFAC10) complex. Downregulation of AK2 attenuates etoposide- or staurosporine-induced apoptosis in human cells, but not that induced by tumour-necrosis-factor-related apoptosis-inducing ligand ( TRAIL) or Fas ligand ( FasL). During intrinsic apoptosis, AK2 translocates to the cytoplasm, whereas this event is diminished in Apaf-1 knockdown cells and prevented by Bcl-2 or Bcl-X-L. Addition of purified AK2 protein to cell extracts first induces activation of caspase-10 via FADD and subsequently caspase-3 activation, but does not affect caspase-8. AFAC10 complexes are detected in cells undergoing intrinsic cell death and AK2 promotes the association of caspase-10 with FADD. In contrast, AFAC10 complexes are not detected in several etoposide-resistant human tumour cell lines. Taken together, these results suggest that, acting in concert with FADD and caspase-10, AK2 mediates a novel intrinsic apoptotic pathway that may be involved in tumorigenesis. English NATURE PUBLISHING GROUP AK2 activates a novel apoptotic pathway through formation of a complex with FADD and caspase-10 Article 10.1038/ncb1650 1 NATURE CELL BIOLOGY, v.9, no.11, pp.1303 - U176 NATURE CELL BIOLOGY 9 11 1303 U176 N scie scopus 000250659600016 2-s2.0-35748962612 Cell Biology Cell Biology Article FAS-ASSOCIATED PROTEIN DEATH DOMAIN ADENYLATE KINASE MEDIATED APOPTOSIS CYTOCHROME-C CELL-DEATH PHOSPHORYLATION FADD/MORT1 RECEPTOR PERMEABILIZATION