New research details how lysosomes – the structures inside cells that degrade and recycle waste -- change their protein composition as organisms become long-lived, providing new insights into the role these organelles and their associated proteins play in regulating longevity.

Lysosomes have historically been seen as the scavenger centers of the cell, but recent research has shown these organelles also play a key role in coordinating cellular metabolism with signals originating both within and outside the cell. These processes, which have been linked to regulating how long organisms live, may be mediated by proteins associated with the lysosome.

In a new study, led by Janelia Senior Group Leader Meng Wang, researchers set out to gain a systematic understanding of how lysosomal proteins change under different longevity conditions, and how these changes contribute to the regulation of longevity.

The researchers used a technique called lysosomal precipitation coupled with deep proteomic profiling to look at all the proteins associated with lysosomes in detail. The team purified lysosomes from different tissues and under different conditions and compared the protein compositions of long-lived and wild-type roundworms.

Using both analysis of the proteins and imaging, they found that for some long-lived conditions the lysosome is closer to the nucleus of the cell. This proximity could aid communication between the two organelles, helping to regulate transcription, which promotes longevity. They also found that crucial nutrition-sensing factors are recruited to the lysosomes under specific long-lived conditions, triggering pro-longevity effects downstream.

The new work provides evidence that lysosomes are not static organelles -- they dynamically change their protein composition in response to the environment and the cell’s metabolism, which could initiate a signaling chain that ultimately affects the organism’s health and longevity.

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Citation:

Yong Yu, Shihong M Gao, Youchen Guan, Pei-Wen Hu, Qinghao Zhang, Jiaming Liu, Bentian Jing, Qian Zhao, David M Sabatini, Monther Abu-Remaileh, Sung Yun Jung, Meng C Wang. “Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.” eLife. February 19, 2024. DOI: 10.7554/eLife.85214