Autophagy genes in biology and disease

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(6), P. 382 - 400

Published: Jan. 12, 2023

Language: Английский

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Autophagy in Alzheimer’s disease pathogenesis: Therapeutic potential and future perspectives

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 72, P. 101464 - 101464

Published: Sept. 20, 2021

Alzheimer's disease (AD) is a complex neurodegenerative in the elderly and most common cause of human dementia. AD characterized by accumulation abnormal protein aggregates including amyloid plaques (composed beta-amyloid (Aβ) peptides) neurofibrillary tangles (formed hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction patients. Autophagy an evolutionarily conserved lysosome-dependent cellular event eukaryotes. It closely linked to modulation metabolism, through which damaged organelles mis-folded proteins are degraded then recycled maintain homeostasis. Accumulating evidence has shown that impaired autophagy contributes pathogenesis. In present review, we highlight role autophagy, bulk selective regulating metabolic circuits We discuss potential future perspectives autophagy-inducing strategies therapeutics.

Language: Английский

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Autophagy and the hallmarks of aging

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 72, P. 101468 - 101468

Published: Sept. 24, 2021

Language: Английский

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Autophagy in age-related macular degeneration

Autophagy, Journal Year: 2022, Volume and Issue: 19(2), P. 388 - 400

Published: April 25, 2022

Age-related macular degeneration (AMD) is the leading cause of visual impairment in aging population with limited understanding its pathogenesis and a lack effective treatment. The progression AMD initially characterized by atrophic alterations retinal pigment epithelium, as well formation lysosomal lipofuscin extracellular drusen deposits. Damage caused chronic oxidative stress, protein aggregation inflammatory processes may lead to geographic atrophy and/or choroidal neovascularization fibrosis. role macroautophagy/autophagy pathology steadily emerging. This review describes selective secretory autophagy their biogenesis, senescence-associated phenotype, inflammation epithelial-mesenchymal transition AMD.

Language: Английский

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Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Sept. 29, 2021

Removal of damaged organelles via the process selective autophagy constitutes a major form cellular quality control. Damaged are recognized by dedicated surveillance machinery, leading to assembly an autophagosome around organelle, prior fusion with degradative lysosomal compartment. Lysosomes themselves also prone damage and degraded through lysophagy. While early steps involve recognition ruptured membranes glycan-binding galectins ubiquitylation transmembrane proteins, many in process, their interrelationships, remain poorly understood, including role identity cargo receptors required for completion Here, we employ quantitative organelle capture proximity biotinylation proteomics adaptors, receptors, response acute damage, thereby revealing landscape lysosome-associated proteome remodeling during Among proteins dynamically recruited lysosomes were ubiquitin-binding autophagic receptors. Using newly developed lysophagic flux reporters Lyso-Keima, demonstrate that TAX1BP1, together its associated kinase TBK1, both necessary sufficient promote HeLa cells induced neurons (iNeurons). related receptor Optineurin (OPTN) can drive damage-dependent lysophagy when overexpressed, lacking either OPTN or CALCOCO2 still maintain significant cells. Mechanistically, TAX1BP1-driven requires N-terminal SKICH domain, which binds TBK1 regulatory factor RB1CC1, upstream events efficient recruitment flux. These results identify TAX1BP1 as central component pathway provide proteomic resource future studies process.

Language: Английский

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ER-phagy: mechanisms, regulation, and diseases connected to the lysosomal clearance of the endoplasmic reticulum

Physiological Reviews, Journal Year: 2022, Volume and Issue: 102(3), P. 1393 - 1448

Published: Feb. 21, 2022

ER-phagy (reticulophagy) defines the degradation of portions endoplasmic reticulum (ER) within lysosomes or vacuoles. It is part self-digestion (i.e., autophagic) programs recycling cytoplasmic material and organelles, which rapidly mobilize metabolites in cells confronted with nutrient shortage. Moreover, selective clearance ER subdomains participates control size activity during stress, reestablishment homeostasis after stress resolution, removal parts aberrant potentially cytotoxic has been segregated. relies on individual and/or concerted activation receptors, peripheral integral membrane proteins that share presence LC3/Atg8-binding motifs their cytosolic domains. involves physical separation from bulk network delivery to endolysosomal/vacuolar catabolic district. This last step accomplished by a variety mechanisms including macro-ER-phagy (in fragments are sequestered double-membrane autophagosomes eventually fuse lysosomes/vacuoles), micro-ER-phagy directly engulfed endosomes/lysosomes/vacuoles), direct fusion ER-derived vesicles lysosomes/vacuoles. dysfunctional specific human diseases, its regulators subverted pathogens, highlighting crucial role for cell organism life.

Language: Английский

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Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

As the essential regulators of organ fibrosis, macrophages undergo marked phenotypic and functional changes after injury. These in macrophage phenotype function can result maladaptive repair, causing chronic inflammation development pathological fibrosis. Autophagy, a highly conserved lysosomal degradation pathway, is one major players to maintain homeostasis through clearing protein aggregates, damaged organelles, invading pathogens. Emerging evidence has shown that autophagy plays an role polarization, inflammation, Because high heterogeneity different organs, types may play roles Here, we review current understanding fibrosis highlight potential treatment Finally, important unresolved issues this field are briefly discussed. A better mechanisms contribute developing novel therapies for inflammatory diseases

Language: Английский

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Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

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Orchestration of selective autophagy by cargo receptors

Current Biology, Journal Year: 2022, Volume and Issue: 32(24), P. R1357 - R1371

Published: Dec. 1, 2022

Cellular homeostasis requires the swift and specific removal of damaged material. Selective autophagy represents a major pathway for degradation such cargo This is achieved by sequestration within double-membrane vesicles termed autophagosomes, which form de novo around subsequently deliver their content to lysosomes degradation. The importance selective exemplified various neurodegenerative diseases associated with defects in this pathway, including Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia. It has become evident that receptors are acting as Swiss army knives recognizing cargo, orchestrating recruitment machinery autophagosome biogenesis, closely aligning membrane cargo. Furthermore, sequester ubiquitinated proteins into larger condensates upstream induction. Here, we review recent insights mechanisms action focusing on roles sequestosome-like misfolded, mitochondria. We also highlight at steps function result accumulation harmful material how knowledge may guide design future therapies.

Language: Английский

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Molecular regulation of autophagosome formation

Biochemical Society Transactions, Journal Year: 2022, Volume and Issue: 50(1), P. 55 - 69

Published: Jan. 25, 2022

Macroautophagy, hereafter autophagy, is a degradative process conserved among eukaryotes, which essential to maintain cellular homeostasis. Defects in autophagy lead numerous human diseases, including various types of cancer and neurodegenerative disorders. The hallmark the de novo formation autophagosomes, are double-membrane vesicles that sequester deliver cytoplasmic materials lysosomes/vacuoles for degradation. mechanism autophagosome biogenesis entered molecular era with identification autophagy-related (ATG) proteins. Although there many unanswered questions aspects have raised some controversies, enormous advances been done our understanding recent years. In this review, we describe current knowledge about regulation formation, particular focus on budding yeast mammalian cells.

Language: Английский

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