4.6 Review

Regulation of the lysosome by sphingolipids: Potential role in aging

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 298, Issue 7, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.jbc.2022.102118

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Funding

  1. National Natural Science Foundation of China [32071163, 32070754]
  2. Natural Sci- ence Foundation of Chongqing, China [cstc2021ycjh- bgzxm0138, cstc2020jcyj-msxmX0714]

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Sphingolipids are closely associated with aging and aging-related diseases, and they control aging by regulating lysosomal homeostasis and function. Studies show that sphingolipid-related diseases and aging share common mechanisms, potentially regulated through the lysosome.
Sphingolipids are a class of bioactive complex lipids that have been closely associated with aging and aging-related diseases. However, the mechanism through which sphingolipids control aging has long been a mystery. Emerging studies reveal that sphingolipids exert tight control over lysosomal homeostasis and function, as evidenced by sphingolipid-related diseases, including but not limited to lysosomal storage disorders. These diseases are defined by primary lysosomal defects and a few secondary defects such as mitochondrial dysfunction. Intriguingly, recent research indicates that the majority of these defects are also associated with aging, implying that sphingolipid-related diseases and aging may share common mechanisms. We propose that the lysosome is a pivotal hub for sphingolipid-mediated aging regulation. This review discusses the critical roles of sphingolipid metabolism in regulating various lysosomal functions, with an emphasis on how such regulation may contribute to aging and aging-related diseases.

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