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Lysosome dysfunction in the pathogenesis of kidney diseases

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Abstract

The lysosome, an organelle central to macromolecule degradation and recycling, plays a pivotal role in normal cell processes, ranging from autophagy to redox regulation. Not surprisingly, lysosomes are an integral part of the renal epithelial molecular machinery that facilitates normal renal physiology. Two inherited diseases that manifest as kidney dysfunction are Fabry’s disease and cystinosis, each of which is caused by a primary biochemical defect at the lysosome resulting from loss-of-function mutations in genes that encode lysosomal proteins. The functions of the lysosomes in the kidney and how lysosomal dysfunction might contribute to Fabry’s disease and cystinosis are discussed. Unlike most other pediatric renal diseases, therapies are available for Fabry’s disease and cystinosis, but require early diagnosis. Recent analysis of ceroid neuronal lipofuscinosis type 3 (Cln3) null mice, a mouse model of lysosomal disease that is primarily associated with neurological deficits, revealed renal functional abnormalities. As current and future therapeutics increase the life-span of those suffering from diseases like neuronal ceroid lipofuscinosis, it remains a distinct possibility that many more lysosomal disorders that primarily manifest as infant and juvenile neurodegenerative diseases may also include renal disease phenotypes.

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Acknowledgements

Partially supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number 1P20GM103620-01A1 (Pediatrics) and by Sanford Health.

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  1. Sanford Children’s Health Research Center, Sanford Research/USD, Sioux Falls, SD, 57104, USA

    Kameswaran Surendran, Seasson P. Vitiello & David A. Pearce

  2. Department of Pediatrics, Sanford School of Medicine, Sioux Falls, SD, 57104, USA

    Kameswaran Surendran & David A. Pearce

  3. Augustana College, Sioux Falls, SD, USA

    Seasson P. Vitiello

  4. Sanford Research/USD, 2301 East 60th Street North, Sioux Falls, SD, 57104-0589, USA

    David A. Pearce

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Surendran, K., Vitiello, S.P. & Pearce, D.A. Lysosome dysfunction in the pathogenesis of kidney diseases. Pediatr Nephrol 29, 2253–2261 (2014). https://doi.org/10.1007/s00467-013-2652-z

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