Dysregulation of autophagy as a common mechanism in lysosomal storage diseases DOI Creative Commons

Elena Seranova,

Kyle J. Connolly, Malgorzata Zatyka

et al.

Essays in Biochemistry, Journal Year: 2017, Volume and Issue: 61(6), P. 733 - 749

Published: Dec. 12, 2017

The lysosome plays a pivotal role between catabolic and anabolic processes as the nexus for signalling pathways responsive to variety of factors, such growth, nutrient availability, energetic status cellular stressors. Lysosomes are also terminal degradative organelles autophagy through which macromolecules damaged components degraded. Autophagy acts homeostatic pathway that is essential organismal physiology. Decline in during ageing or many diseases, including late-onset forms neurodegeneration considered major contributing factor pathology. Multiple lines evidence indicate impairment central mechanism underlying several lysosomal storage disorders (LSDs). LSDs class rare, inherited whose histopathological hallmark accumulation undegraded materials lysosomes due abnormal function. Inefficient capability has negative impact on flux autophagic pathway, therefore dysregulated emerging relevant disease mechanism. Pathology generally early-onset, severe life-limiting but current therapies limited absent; recognizing common defects raises new possibilities therapy. In this review, we describe mechanisms by occur, focusing perturbations present latest data supporting development novel therapeutic approaches related modulation autophagy.

Language: Английский

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1 DOI Creative Commons

Daniel J. Klionsky,

Amal Kamal Abdel‐Aziz, Sara Abdelfatah

et al.

Autophagy, Journal Year: 2021, Volume and Issue: 17(1), P. 1 - 382

Published: Jan. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Language: Английский

Citations

2014

Compromised autophagy and neurodegenerative diseases DOI

Fiona M. Menzies,

Angeleen Fleming, David C. Rubinsztein

et al.

Nature reviews. Neuroscience, Journal Year: 2015, Volume and Issue: 16(6), P. 345 - 357

Published: May 20, 2015

Language: Английский

Citations

760

Development of autophagy inducers in clinical medicine DOI Open Access
Beth Levine,

Milton Packer,

Patrice Codogno

et al.

Journal of Clinical Investigation, Journal Year: 2015, Volume and Issue: 125(1), P. 14 - 24

Published: Jan. 1, 2015

Defects in autophagy have been linked to a wide range of medical illnesses, including cancer as well infectious, neurodegenerative, inflammatory, and metabolic diseases. These observations led the hypothesis that inducers may prevent or treat certain clinical conditions. Lifestyle nutritional factors, such exercise caloric restriction, exert their known health benefits through pathway. Several currently available FDA-approved drugs shown enhance autophagy, this autophagy-enhancing action be repurposed for use novel indications. The development new are designed more selective function target organs is expected maximize while minimizing toxicity. This Review summarizes rationale current approaches developing medicine, factors considered defining disease targets therapy, potential treatment human health.

Language: Английский

Citations

312

ER–lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann–Pick type C DOI

Chun-Yan Lim,

Oliver B. Davis, Hijai R. Shin

et al.

Nature Cell Biology, Journal Year: 2019, Volume and Issue: 21(10), P. 1206 - 1218

Published: Sept. 23, 2019

Language: Английский

Citations

262

Autophagy in liver diseases: A review DOI
Hui Qian, Xiaojuan Chao, Jessica A. Williams

et al.

Molecular Aspects of Medicine, Journal Year: 2021, Volume and Issue: 82, P. 100973 - 100973

Published: June 11, 2021

Language: Английский

Citations

256

Autophagosome-Lysosome Fusion DOI Creative Commons
Péter Lőrincz, Gábor Juhász

Journal of Molecular Biology, Journal Year: 2019, Volume and Issue: 432(8), P. 2462 - 2482

Published: Nov. 2, 2019

Macroautophagy is a conserved catabolic process observed in all eukaryotic cells, during which selected cellular components are transported to and broken down within lysosomes. The starts with the capture of unnecessary material into autophagosomes, followed by autophagosome-lysosome fusion generate autolysosomes that degrade cargo. In past quarter-century, our knowledge about autophagosome formation almost exponentially increased, while later steps were much less studied. This fortunately changed few years, more publications focusing on fate completed autophagosome. this review, we aspire summarize current molecular mechanisms fusion.

Language: Английский

Citations

250

A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy DOI Creative Commons
Rekha Khandia, Maryam Dadar, Ashok Munjal

et al.

Cells, Journal Year: 2019, Volume and Issue: 8(7), P. 674 - 674

Published: July 3, 2019

Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, infection-mediated stresses. dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, neurodegeneration. This review describes the mechanisms of autophagy its associations with other cell death mechanisms, apoptosis, necrosis, necroptosis, autosis. has both positive negative infection, cancer, neural development, metabolism, cardiovascular health, immunity, iron homeostasis. Genetic defects such as static childhood encephalopathy neurodegeneration adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon X-linked myopathy excessive autophagy, sporadic inclusion body myositis. Further studies on different microbial infections could help to design develop novel therapeutic strategies against pathogenic microbes. progress prospects research activators suppressors, which be used intervention numerous diseases drugs protect human animal health.

Language: Английский

Citations

244

Complex lipid trafficking in Niemann‐Pick disease type C DOI

Marie T. Vanier

Journal of Inherited Metabolic Disease, Journal Year: 2014, Volume and Issue: 38(1), P. 187 - 199

Published: Nov. 26, 2014

Language: Английский

Citations

239

Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle DOI
Anna Vainshtein,

Liam D. Tryon,

Marion Pauly

et al.

AJP Cell Physiology, Journal Year: 2015, Volume and Issue: 308(9), P. C710 - C719

Published: Feb. 12, 2015

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase demands initiate mitochondrial biogenesis, orchestrated by transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about degradation mitochondria following although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, exercise-induced adaptations. How mitophagy activated and what role PGC-1α plays this process during have yet be evaluated. Thus we investigated autophagy/mitophagy muscle immediately an bout or 90 min wild-type (WT) knockout (KO) animals. Deletion resulted 40% decrease content, as well 25% decline running performance, was accompanied severe acidosis KO animals, indicating distress. Exercise induced significant increases gene transcripts various (e.g., cytochrome oxidase subunit IV transcription factor A) autophagy-related p62 light chain 3) genes WT, but not KO, also enhanced targeting for mitophagy, increased autophagy flux, WT This effect attenuated absence PGC-1α. We identified Niemann-Pick C1, transmembrane protein involved lysosomal lipid trafficking, target that with exercise. These results suggest turnover at least part coordinated Anna Vainshtein received AJP-Cell 2015 Paper Year award. Listen podcast coauthor David A. Hood http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .

Language: Английский

Citations

239

Emerging Roles for the Lysosome in Lipid Metabolism DOI
Ashley M. Thelen, Roberto Zoncu

Trends in Cell Biology, Journal Year: 2017, Volume and Issue: 27(11), P. 833 - 850

Published: Aug. 30, 2017

Language: Английский

Citations

233