Survey of the human proteostasis network: the autophagy-lysosome pathway

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis is the province of the proteostasis network, a highly interconnected system of over 3000 components that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental functional unit in biology that is essential for cellular health and has direct relevance to many diseases of protein conformation. However, it is not well defined or annotated, hindering its functional characterization in health and disease. In this series of manuscripts, we aim to operationally define the human proteostasis network by providing a comprehensive, annotated list of its components. In the other manuscripts in this series, we survey the components of the proteostasis network that make up (1) the machineries for protein synthesis, protein folding, protein trafficking into and out of organelles, and organelle-specific degradation pathways and (2) the ubiquitin-proteasome system. Here, we have compiled a curated list of over 850 unique high-confidence components of the autophagy-lysosome pathway, the other major protein degradation system in human cells. This resource will facilitate the rigorous investigation of autophagy-lysosome pathway dysfunction as a driver of proteostasis imbalance in aging and disease.

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Publication Details

Journal
Autophagy
Published
2026-10-28
DOI
https://doi.org/10.1080/15548627.2026.2741038
Citations
1
Primary Topic
Autophagy in Disease and Therapy
Type
article
Field-Weighted Citation Impact
4.66

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article

Survey of the human proteostasis network: the autophagy-lysosome pathway

Richard I. Morimoto, Ching‐Chieh Chou, Vincent B. Masto, Beatrice Costa et al.
1 citations
Autophagy
Autophagy in Disease and Therapy
4.66
article

Survey of the human proteostasis network: the autophagy-lysosome pathway

Richard I. Morimoto, Ching‐Chieh Chou, Vincent B. Masto, Beatrice Costa, Thomas Stoeger, Lisa P. Elia, Eugenia M. Clérico, Patricia Martínez-Botía, Miguel A. Prado, Ralph A. Nixon, Shijie Wang, Rajshri Iyer, Reese A. K. Richardson, Ee Phie Tan, Alejandro Rodríguez Gama, T. Kelly Rainbolt, Judith Frydman, Steven M. Finkbeiner, Xiaojing Sui, Jason E. Gestwicki, Evan T. Powers, Suzanne Elsasser, Maher Budron, Eric Mockler, Jeffery W. Kelly, Bianca Herting, Zachary Tokuno, Daniel J. Finley, Lynée A. Massey, Dan Garza, Christian M. Cole, Qiang Xiao, Roy D. Kurtzbard
article en
1 citations

Abstract

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis is the province of the proteostasis network, a highly interconnected system of over 3000 components that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental functional unit in biology that is essential for cellular health and has direct relevance to many diseases of protein conformation. However, it is not well defined or annotated, hindering its functional characterization in health and disease. In this series of manuscripts, we aim to operationally define the human proteostasis network by providing a comprehensive, annotated list of its components. In the other manuscripts in this series, we survey the components of the proteostasis network that make up (1) the machineries for protein synthesis, protein folding, protein trafficking into and out of organelles, and organelle-specific degradation pathways and (2) the ubiquitin-proteasome system. Here, we have compiled a curated list of over 850 unique high-confidence components of the autophagy-lysosome pathway, the other major protein degradation system in human cells. This resource will facilitate the rigorous investigation of autophagy-lysosome pathway dysfunction as a driver of proteostasis imbalance in aging and disease.

Autophagy
Northwestern University (US), Scripps Research Institute (US), Nathan Kline Institute for Psychiatric Research (US), Gladstone Institutes (US), Harvard University (US), University of Arizona (US), University of California, San Francisco (US), University of Cambridge (GB), Taube Koret Center (US), MRC Toxicology Unit (GB), Instituto de Investigación Sanitaria del Principado de Asturias (ES), New York University (US), Stanford University (US)
Hevolution Foundation, U.S. Department of Defense, European Commission, National Institutes of Health, Instituto de Salud Carlos III
Good health and well-being
Openalex Percentile: Top 4%
Autophagy in Disease and Therapy
4.66
DOIOpen Access PDFOpenAlex
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