bims-unfpre Biomed News
on Unfolded protein response
Issue of 2019‒09‒01
two papers selected by
Susan Logue
University of Manitoba

  1. Elife. 2019 Aug 27. pii: e47084. [Epub ahead of print]8
    Shemorry A, Harnoss JM, Guttman O, Marsters SA, Kőműves LG, Lawrence DA, Ashkenazi A.
      Upon detecting endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) orchestrates adaptive cellular changes to reestablish homeostasis. If stress resolution fails, the UPR commits the cell to apoptotic death. Here we show that in hematopoietic cells, including multiple myeloma (MM), lymphoma, and leukemia cell lines, ER stress leads to caspase-mediated cleavage of the key UPR sensor IRE1 within its cytoplasmic linker region, generating a stable IRE1 fragment comprising the ER-lumenal domain and transmembrane segment (LDTM). This cleavage uncouples the stress-sensing and signaling domains of IRE1, attenuating its activation upon ER perturbation. Surprisingly, LDTM exerts negative feedback over apoptotic signaling by inhibiting recruitment of the key proapoptotic protein BAX to mitochondria. Furthermore, ectopic LDTM expression enhances xenograft growth of MM tumors in mice. These results uncover an unexpected mechanism of cross-regulation between the apoptotic caspase machinery and the UPR, which has biologically significant consequences for cell survival under ER stress.
    Keywords:  BAX; XBP1; apoptosis; cancer; cancer biology; cell biology; hematopoietic; human; mouse; myeloma
  2. Trends Endocrinol Metab. 2019 Aug 24. pii: S1043-2760(19)30159-6. [Epub ahead of print]
    Quintana-Cabrera R, Soriano ME.
      Assembly factors are necessary for the formation of mitochondrial supercomplexes (SCs) and in making cellular respiration more efficient. In a recent study, Balsa et al. (Mol. Cell, 2019) report that nutrient-induced endoplasmic reticulum (ER) stress engages PERK-eIF2α-mediated transcription of the SCs assembly factor SCAF1, events that coordinate ER stress and SCs formation to improve bioenergetics.
    Keywords:  ER stress; SCAF1; glucose deprivation; mitochondrial cristae; supercomplexes