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

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Abstract

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.

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Funding

We gratefully acknowledge research support from the National Institute of General Medical Sciences under award numbers P30GM100329 and U54GM115458, the National Institute of Mental Health under award numbers R01MH100972 and R01MH105329, the National Institute of Neurological Diseases and Stroke (NINDS) under award number R01NS065957, and the National Institute of Drug Abuse under award number R01DA032444. The authors would like to thank Parinaz Ghanbari for designing illustrations contained in this manuscript.

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  1. Department of Biomedical Sciences, Dakota School of Medicine and Health Sciences, University of North, Grand Forks, ND, 58203, USA

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

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  1. Koffi L. Lakpa
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  2. Nabab Khan
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  3. Zahra Afghah
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  4. Xuesong Chen
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  5. Jonathan D. Geiger
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Correspondence to Jonathan D. Geiger.

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Lakpa, K.L., Khan, N., Afghah, Z. et al. Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance. J Neuroimmune Pharmacol 16, 219–237 (2021). https://doi.org/10.1007/s11481-021-09990-7

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