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Biological Functions of Autophagy Genes: A Disease Perspective
Open accessAbstract
The lysosomal degradation pathway of autophagy plays a fundamental role in cellular, tissue, and organismal homeostasis and is mediated by evolutionarily conserved autophagy-related (ATG) genes. Definitive etiological links exist between mutations in genes that control autophagy and human disease, especially neurodegenerative, inflammatory disorders and cancer. Autophagy selectively targets dysfunctional organelles, intracellular microbes, and pathogenic proteins, and deficiencies in these processes may lead to disease. Moreover, ATG genes have diverse physiologically important roles in other membrane-trafficking and signaling pathways. This Review discusses the biological functions of autophagy genes from the perspective of understanding-and potentially reversing-the pathophysiology of human disease and aging.
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“In patients, loss-of-function mutations of genes that regulate or execute autophagy have been causally linked to a broad spectrum of cardiovascular, infectious, neurodegenerative, metabolic, musculoskeletal, ocular and pulmonary disorders, many of which resemble to premature aging at the histopathological and functional levels 89,90 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [89]
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“Protein aggregates can also be removed by macroautophagy upon their inclusion in two-membrane vesicles, the autophagosomes, for their later fusion with lysosomes 89 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [89]
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“There is consistency in the literature about the beneficial role of green tea on senescence-related mechanisms, thanks to its scavenging properties against ROS and RNS and its ability to stimulate autophagy [279,280,281,282].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [282]
In the citing paper
“For this reason, baseline autophagy is required for the maintenance of cellular and organismal fitness”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [146]
In the citing paper
“Fusion of autophagosomes with lysosomes requires microtubule-based transport, tethering factors, and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein [SNAP] receptor) proteins (Leidal et al., 2018; Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Levine and Kroemer, 2019
In the citing paper
“In autophagy, damaged organelles (e.g., mitochondria, lysosomes, peroxisomes) and cellular material (e.g., proteins, lipids, nucleic acids) are enclosed in a double-membraned autophagosome and delivered to lysosomes for degradation (Leidal et al., 2018; Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Levine and Kroemer, 2019
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“However, prolonged stress downregulates autophagy, which could send the cell into a spiral of increased debris, mitochondrial injury, and eventual metabolic reprogramming (Leidal et al., 2018; Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Levine and Kroemer, 2019
In the citing paper
“These include syntaxin-17 on autophagosomes and vesicle-associated membrane protein (VAMP) 7/8 on endolysosomal membranes (Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Levine and Kroemer, 2019
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4 retracted
RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
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RetractedRepertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
mTOR Signaling in Growth, Metabolism, and Disease
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Autophagy in the Pathogenesis of Disease
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Self-citationAutophagy: Renovation of Cells and Tissues
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A role for mitochondria in nlrp3 inflammasome activation
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Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
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Metadata
- Authors
- Levine, B., & Kroemer, G.
- Affiliations
- Howard Hughes Medical Institute (US)
- Karolinska University Hospital (SE)
- Corresponding author
- Levine, Beth
- Kroemer, Guido
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 176
- Issue
- 1-2
- Pages
- 11-42
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6347410
- OpenAlex
- W2909477364
- Cited by
- 2,832
- References
- 311
- Citations by year
- 2026: 254 · 2025: 399 · 2024: 477 · 2023: 456 · 2022: 403 · 2021: 414 · 2020: 292 · 2019: 135
- FWCI
- 46.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- NIH (RO1 CA109618, U19 AI109725)
- Cancer Prevention Research Institute of Texas (RP120718)
- Fondation Leducq (15CBD04)
- Ligue contre le Cancer
- Agence National de la Recherche
- Association pour la recherche sur le cancer
- Cancéropôle Ile-de-France
- Chancelerie des universités de Paris
- Fondation pour la Recherche Médicale
- European Research Area Network on Cardiovascular Diseases
- European Research Council
- Fondation Carrefour
- Institut National du Cancer
- Inserm
- Institut Universitaire de France
- LabEx Immuno-Oncology
- RHU Torino Lumière
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination
- SIRIC Cancer Research and Personalized Medicine
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- autophagy, autophagy-related genes, lysosomal degradation, neurodegenerative diseases, inflammatory diseases, cancer, aging, membrane trafficking, selective autophagy, organelle degradation, disease pathophysiology
- MeSH terms
- Autophagy-Related Proteins, Animals, Autophagy, Homeostasis, Humans, Lysosomes, Proteins, Signal Transduction, Neurodegenerative Diseases
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