Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance

Koffi L. Lakpa, Nabab Khan, Zahra Afghah, Xuesong Chen, Jonathan D. Geiger

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


Extensive work has characterized endoplasmic reticulum (ER) and mitochondrial stress responses. In contrast, very little has been published about stress responses in lysosomes; subcellular acidic organelles that are physiologically important and are of pathological relevance. The greater lysosomal system is dynamic and is comprised of endosomes, lysosomes, multivesicular bodies, autophagosomes, and autophagolysosomes. They are important regulators of cellular physiology, they represent about 5% of the total cellular volume, they are heterogeneous in their sizes and distribution patterns, they are electron dense, and their subcellular positioning within cells varies in response to stimuli, insults and pH. These organelles are also integral to the pathogenesis of lysosomal storage diseases and it is increasingly recognized that lysosomes play important roles in the pathogenesis of such diverse conditions as neurodegenerative disorders and cancer. The purpose of this review is to focus attention on lysosomal stress responses (LSR), compare LSR with better characterized stress responses in ER and mitochondria, and form a framework for future characterizations of LSR. We synthesized data into the concept of LSR and present it here such that the definition of LSR can be modified as new knowledge is added and specific therapeutics are developed. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)219-237
Number of pages19
JournalJournal of Neuroimmune Pharmacology
Issue number2
StatePublished - Jun 2021


  • Endoplasmic reticulum stress
  • Endosomes
  • Inter-organellar signaling
  • Lysosomes
  • Mitochondrial stress

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology


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