bims-lycede Biomed News
on Lysosome-dependent cell death
Issue of 2026–06–21
three papers selected by
Sofía Peralta, Universidad Nacional de Cuyo
  1. Substrate selectivity as a paradigm shift in mTORC1 signaling.
  2. A comprehensive in silico investigation into the deleterious nonsynonymous single nucleotide polymorphisms of the human transcription factor EB (TFEB) gene and their predicted association with cancer.
  3. Lysosome: not only for digestion but also for production.
  1. Curr Opin Cell Biol. 2026 Jun 17. pii: S0955-0674(26)00052-9. [Epub ahead of print]101 102664
    Substrate selectivity as a paradigm shift in mTORC1 signaling.
    Jiyoung Pan, Stephanie A Fernandes, Riko Hatakeyama, Constantinos Demetriades.
      mTORC1 is a central regulator of cell growth and metabolism, classically viewed as a binary switch that promotes anabolic programs while suppressing catabolic pathways. Recent work advances this simplified model by revealing that mTORC1 signaling is highly substrate-specific, with distinct classes of substrates differentially regulated according to their modes of recruitment and subcellular localization. In this review, we discuss emerging evidence demonstrating that mTORC1 activity and its lysosomal localization can be functionally uncoupled, enabling selective phosphorylation of lysosomal versus non-lysosomal targets. We highlight how upstream regulatory pathways and post-translational modifications shape these substrate-specific outputs, and consider the implications of downstream uncoupling for the fundamental understanding of mTORC1 biology as well as human health and disease.
    DOI:  https://doi.org/10.1016/j.ceb.2026.102664
  2. J Genet Eng Biotechnol. 2026 Jun;pii: S1687-157X(26)00030-2. [Epub ahead of print]24(2): 100686
    A comprehensive in silico investigation into the deleterious nonsynonymous single nucleotide polymorphisms of the human transcription factor EB (TFEB) gene and their predicted association with cancer.
    Mohtasim Fuad, Sadia Akter, Zimam Mahmud, Sonia Tamanna, Mohammad Sayem, Abm Reazul Islam Zim, Md Zakir Hossain Howlader.
      Transcription factor EB (TFEB) is an essential protein that is connected to a number of diseases, such as lysosomal storage disorders and cancer. Patients with glioblastoma multiforme and uterine endometrioid carcinoma have already been identified to have nonsynonymous mutations in this gene. These mutations may have an impact on TFEB protein's functions and structure. Therefore, to find possible biomarkers for different disease treatments, the most harmful single nucleotide polymorphisms (SNPs) of the TFEBprotein have been identified in this study. The goal is to create a systematic dataset of the SNPs related to the TFEBgene, which could be useful in the diagnosis and management of many disorders linked to the target gene. The SNPs of the TFEBprotein were analyzed via a wide range of bioinformatics techniques, including both sequence and structure-based methodologies. Nonsynonymous SNV research can be advanced through the application of various machine learning methods that have been developed as a result of recent advancements in computational platforms. Among 449 nsSNPs, a total of 6 nsSNPs have been found to be harmful, destabilizing, and disease-causing. Each nsSNP interferes with its function. All of the mutant proteins interact with the DNA molecule during docking more effectively than the alphafold (wild type) protein does. A strong correlation between cancer and mutations in R315 has been identified. The detrimental effects of nsSNPs and noncoding SNPs on the structure and activities of proteins will help researchers understand the crucial role that mutations play in the molecular pathways involved in a variety of disorders. The discovery of possible targets for the diagnosis of diseases and treatment interventions will eventually result from this. Moreover, this thorough analysis can facilitate the exploration of potential disease-causing SNPs in the TFEB gene and assist in identifying effective drugs or pharmacological targets. Consequently, further experimental mutational research, genome-wide association studies, and clinical-based studies are essential to validate these findings.
    Keywords:  Bioinformatics; Disease-causing mutations; Molecular docking; Non-synonymous mutations; Single nucleotide polymorphisms; TFEB gene
    DOI:  https://doi.org/10.1016/j.jgeb.2026.100686
  3. Life Metab. 2026 Jun;5(3): loag007
    Lysosome: not only for digestion but also for production.
    Life Metabolism Editorial Team
      
    DOI:  https://doi.org/10.1093/lifemeta/loag007
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