bims-iorami 2024-01-21 papers

Issue of 2024–01–21
three papers selected by
Chenxiao Yu, Soochow University

J Cancer Res Clin Oncol. 2024 Jan 18. 150(1): 14

Mitophagy plays a "double-edged sword" role in the radiosensitivity of cancer cells.

Mitochondria are organelles with double-membrane structure of inner and outer membrane, which provides main energy support for cell growth and metabolism. Reactive oxygen species (ROS) mainly comes from mitochondrial and can cause irreversible damage to cells under oxidative stress. Thus, mitochondrial homeostasis is the basis for maintaining the normal physiological function of cells and mitophagy plays a pivotal role in the maintenance of mitochondrial homeostasis. At present, to enhance the sensitivity of cancer cells to radiotherapy and chemotherapy by regulating mitochondria has increasingly become a hot spot of cancer therapy. It is particularly important to study the effect of ionizing radiation (IR) on mitochondria and the role of mitophagy in the radiosensitivity of cancer cells. Most of the existing reviews have focused on mitophagy-related molecules or pathways and the impact of mitophagy on diseases. In this review, we mainly focus on discussing the relationship between mitophagy and radiosensitivity of cancer cells around mitochondria and IR.

Keywords: Cancer; Ionizing radiation; Mitophagy; Radiosensitivity

DOI: https://doi.org/10.1007/s00432-023-05515-2

Cell. 2024 Jan 18. pii: S0092-8674(23)01332-6. [Epub ahead of print]187(2): 235-256

Cell death.

Kim Newton, Andreas Strasser, Nobuhiko Kayagaki, Vishva M Dixit.

Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by eliminating infected cells. Cell death can be induced by the genetically programmed suicide mechanisms of apoptosis, necroptosis, and pyroptosis, or it can be a consequence of dysregulated metabolism, as in ferroptosis. Here, we review the signaling mechanisms underlying each cell-death pathway, discuss how impaired or excessive activation of the distinct cell-death processes can promote disease, and highlight existing and potential therapies for redressing imbalances in cell death in cancer and other diseases.

Keywords: apoptosis; cell death; ferroptosis; necroptosis; pyroptosis

DOI: https://doi.org/10.1016/j.cell.2023.11.044

Nucleic Acids Res. 2024 Jan 15. pii: gkae022. [Epub ahead of print]

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts.

Barbara Trifault, Victoria Mamontova, Giacomo Cossa, Sabina Ganskih, Yuanjie Wei, Julia Hofstetter, Pranjali Bhandare, Apoorva Baluapuri, Blanca Nieto, Daniel Solvie, Carsten P Ade, Peter Gallant, Elmar Wolf, Dorthe H Larsen, Mathias Munschauer, Kaspar Burger.

RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.

DOI: https://doi.org/10.1093/nar/gkae022