Targeting lysosomal quality control as a therapeutic strategy against aging and diseases
- Med Res Rev. 2024 Nov;44(6):2472-2509. doi: 10.1002/med.22047.
- 1. Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
- 2. Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
- 3. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
- 4. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
- 5. Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
- 6. Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Shatin, NT, Hong Kong SAR, China.
- 7. Department of Orthopaedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
- 8. Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, Pennsylvania, USA.
- 9. McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.