Amino acid storage: lysosomal double role in health and disease

Cellular homeostasis depends on a multitude of cellular functions, which in turn depend on the clearance of damaged components for their maintenance. Lysosomes being one of the main sites of recycling, are at the frontline for cellular protein degradation, which leads to generation of protein buildi...

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Main Authors: Aiswarya Raj, Samantha Shrihari, Urmi Bandyopadhyay
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Autophagy Reports
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/27694127.2025.2498324
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author Aiswarya Raj
Samantha Shrihari
Urmi Bandyopadhyay
author_facet Aiswarya Raj
Samantha Shrihari
Urmi Bandyopadhyay
author_sort Aiswarya Raj
collection DOAJ
description Cellular homeostasis depends on a multitude of cellular functions, which in turn depend on the clearance of damaged components for their maintenance. Lysosomes being one of the main sites of recycling, are at the frontline for cellular protein degradation, which leads to generation of protein building blocks, the amino acids (AAs), within the lysosomal lumen. However, the fate of these lysosomal pool of AAs are only partly known. Recently, studies from our and other groups have led to the finding that AA can be stored in lysosomes and revealed a homeostatic communication of these storages with the environment. Thus, lysosome appear to be a nutritional signaling hub that has a dual role. As a degradation-competent hydrolytic sack, lysosomes have a long-studied degradative function, additionally now they can either store or channel into utilization of the AAs generated through their proteolytic activity. Since the existence of a lysosomal AA storage pool has been determined by changing the levels of extracellular AAs, this indicates a multi-directional homeostatic communication between the lysosome and the extracellular environment. This Lysosomal homeostatic and adaptive response to the niche could be vital for life-threatening age-related degenerative disorders, where the lysosome-autophagy pathway and the microenvironmental cues play major roles in the disease progression, which will be discussed further in this piece.
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spelling doaj-art-3e1e0ba3d7314166aa6ebe5baf57cc712025-08-20T03:53:03ZengTaylor & Francis GroupAutophagy Reports2769-41272025-12-014110.1080/27694127.2025.2498324Amino acid storage: lysosomal double role in health and diseaseAiswarya Raj0Samantha Shrihari1Urmi Bandyopadhyay2Manipal Institute of Regenerative Medicine (MIRM), Bengaluru, IndiaManipal Institute of Regenerative Medicine (MIRM), Bengaluru, IndiaManipal Institute of Regenerative Medicine (MIRM), Bengaluru, IndiaCellular homeostasis depends on a multitude of cellular functions, which in turn depend on the clearance of damaged components for their maintenance. Lysosomes being one of the main sites of recycling, are at the frontline for cellular protein degradation, which leads to generation of protein building blocks, the amino acids (AAs), within the lysosomal lumen. However, the fate of these lysosomal pool of AAs are only partly known. Recently, studies from our and other groups have led to the finding that AA can be stored in lysosomes and revealed a homeostatic communication of these storages with the environment. Thus, lysosome appear to be a nutritional signaling hub that has a dual role. As a degradation-competent hydrolytic sack, lysosomes have a long-studied degradative function, additionally now they can either store or channel into utilization of the AAs generated through their proteolytic activity. Since the existence of a lysosomal AA storage pool has been determined by changing the levels of extracellular AAs, this indicates a multi-directional homeostatic communication between the lysosome and the extracellular environment. This Lysosomal homeostatic and adaptive response to the niche could be vital for life-threatening age-related degenerative disorders, where the lysosome-autophagy pathway and the microenvironmental cues play major roles in the disease progression, which will be discussed further in this piece.https://www.tandfonline.com/doi/10.1080/27694127.2025.2498324Lysosomenutrient storageleucineLAMTOR-RAG GTPase complexExtracellular Environment
spellingShingle Aiswarya Raj
Samantha Shrihari
Urmi Bandyopadhyay
Amino acid storage: lysosomal double role in health and disease
Autophagy Reports
Lysosome
nutrient storage
leucine
LAMTOR-RAG GTPase complex
Extracellular Environment
title Amino acid storage: lysosomal double role in health and disease
title_full Amino acid storage: lysosomal double role in health and disease
title_fullStr Amino acid storage: lysosomal double role in health and disease
title_full_unstemmed Amino acid storage: lysosomal double role in health and disease
title_short Amino acid storage: lysosomal double role in health and disease
title_sort amino acid storage lysosomal double role in health and disease
topic Lysosome
nutrient storage
leucine
LAMTOR-RAG GTPase complex
Extracellular Environment
url https://www.tandfonline.com/doi/10.1080/27694127.2025.2498324
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