bims-lycede Biomed News
on Lysosome-dependent cell death
Issue of 2025–03–30
two papers selected by
Sofía Peralta, Universidad Nacional de Cuyo
  1. Lysosomes' fallback strategies: more than just survival or death.
  2. From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications.
  1. Front Cell Dev Biol. 2025 ;13 1559504
    Lysosomes' fallback strategies: more than just survival or death.
    Quan Wang, Ruolin Wang, Haihui Hu, Xiaoqing Huo, Fulong Wang.
      Lysosomes are heterogeneous, acidic organelles whose proper functionality is critically dependent on maintaining the integrity of their membranes and the acidity within their lumen. When subjected to stress, the lysosomal membrane can become permeabilized, posing a significant risk to the organelle's survival and necessitating prompt repair. Although numerous mechanisms for lysosomal repair have been identified in recent years, the progression of lysosome-related diseases is more closely linked to the organelle's alternative strategies when repair mechanisms fail, particularly in the contexts of aging and pathogen infection. This review explores lysosomal responses to damage, including the secretion of lysosomal contents and the interactions with lysosome-associated organelles in the endolysosomal system. Furthermore, it examines the role of organelles outside this system, such as the endoplasmic reticulum (ER) and Golgi apparatus, as auxiliary organelles of the endolysosomal system. These alternative strategies are crucial to understanding disease progression. For instance, the secretion and spread of misfolded proteins play key roles in neurodegenerative disease advancement, while pathogen escape via lysosomal secretion and lysosomotropic drug expulsion underlie cancer treatment resistance. Reexamining these lysosomal fallback strategies could provide new perspectives on lysosomal biology and their contribution to disease progression.
    Keywords:  autophagy; endoplasmic reticulum; exosome; golgi apparatus; lysosomal damage; secretion
    DOI:  https://doi.org/10.3389/fcell.2025.1559504
  2. Biomolecules. 2025 Feb 24. pii: 327. [Epub ahead of print]15(3):
    From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications.
    Adel A Alhowyan, Gamaleldin I Harisa.
      Lysosomes are essential intracellular organelles involved in plentiful cellular processes such as cell signaling, metabolism, growth, apoptosis, autophagy, protein processing, and maintaining cellular homeostasis. Their dysfunction is linked to various diseases, including lysosomal storage disorders, inflammation, cancer, cardiovascular diseases, neurodegenerative conditions, and aging. This review focuses on current and emerging therapies for lysosomal diseases (LDs), including small medicines, enzyme replacement therapy (ERT), gene therapy, transplantation, and lysosomal drug targeting (LDT). This study was conducted through databases like PubMed, Google Scholar, Science Direct, and other research engines. To treat LDs, medicines target the lysosomal membrane, acidification processes, cathepsins, calcium signaling, mTOR, and autophagy. Moreover, small-molecule therapies using chaperones, macro-therapies like ERT, gene therapy, and gene editing technologies are used as therapy for LDs. Additionally, endosymbiotic therapy, artificial lysosomes, and lysosomal transplantation are promising options for LD management. LDT enhances the therapeutic outcomes in LDs. Extracellular vesicles and mannose-6-phosphate-tagged nanocarriers display promising approaches for improving LDT. This study concluded that lysosomes play a crucial role in the pathophysiology of numerous diseases. Thus, restoring lysosomal function is essential for treating a wide range of conditions. Despite endosymbiotic therapy, artificial lysosomes, lysosomal transplantation, and LDT offering significant potential for LD control, there are ample challenges regarding safety and ethical implications.
    Keywords:  LDT; engineered lysosome; enzyme replacement therapy; gene therapy; lysosomal diseases; proteopathy
    DOI:  https://doi.org/10.3390/biom15030327
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