The different autophagy degradation pathways and neurodegeneration

Fleming, Angeleen; Bourdenx, Mathieu; Fujimaki, Mitsuhisa; Karabiyik, Cansu; Krause, Gregory J.; López, Ana; Martín‐Segura, Adrián; Puri, Claudia; Scrivo, Aurora; Skidmore, John; Son, Sungmin; Stamatakou, Eleanna; Wróbel, Lidia; Zhu, Ye; Cuervo, Ana María; Rubinsztein, David C.

doi:10.1016/j.neuron.2022.01.017

Cited by 186 publications

(126 citation statements)

References 332 publications

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“…Mitochondria-targeted therapeutic strategies for pathologies associated with aging have received attention due to the effect of enhancing mitochondrial function 12 . Mitophagy maintains neuronal function through maintaining a healthy mitochondrial population and efficient energy supply in the nervous system 23 . Mitophagy inducers such as Kaempferol and Rhapontigenin inhibited memory loss in nematode and rodent models of Alzheimer’s disease through the elimination of dysfunctional mitochondria 24 .…”

Section: Discussionmentioning

confidence: 99%

Urolithin A attenuates auditory cell senescence by activating mitophagy

Cho

Song

2022

Sci Rep

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Aging of sensory organs is associated with a decline in mitochondrial function and the accumulation of dysfunctional mitochondria. Impaired mitophagy blocks the turnover of dysfunctional mitochondria and leads to their accumulation. Urolithin A (UA) induces mitophagy in various mammalian cells. This study was aimed at investigating the effect of the mitophagy activator, UA, on premature senescent auditory cells. The levels of cellular senescence-associated p53 and p21 significantly increased in H2O2-induced senescent House Ear Institute‐Organ of Corti 1 (HEI-OC1) cells and cochlear explants. However, the levels of mitophagy-related molecules significantly decreased. UA significantly decreased the expression of senescence-associated p53 and p21, and increased the expression of mitophagy-related proteins, in H2O2-induced senescent cells and cochlear explants. The percentage of β-galactosidase-stained senescent cells also reduced in H2O2-treated cells and cochlear explants upon UA pre-treatment. The formation of mitophagosomes and mitophagolysosomes was restored upon UA pre-treatment of H2O2-induced senescent cells. The knockdown of mitophagy-related genes (Parkin and Bnip3) resulted in annulment of UA-induced anti-senescent activity. UA significantly increased the ATP content, mitochondrial DNA (mtDNA) integrity, and mitochondrial membrane potential in senescent HEI-OC1 cells. These findings indicate that UA counteracted mitophagy decline and prevented premature senescence in auditory cells. Hence, UA administration might be a promising strategy for preventing mitochondrial dysfunction in patients with age-related hearing loss.

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Section: Discussionmentioning

confidence: 99%

Urolithin A attenuates auditory cell senescence by activating mitophagy

Cho

Song

2022

Sci Rep

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“…By contrast, microautophagy and CMA do not involve any vesicle intermediates. Instead, microautophagy moves cytosolic proteins or endosomal membranes into the lumen of late endosomes via inward membrane invagination, while CMA is believed to translocate cargos directly across the lysosomal membrane with the assistance of an oligomerized type I membrane protein named LAMP2A ( Tekirdag and Cuervo, 2018 ; Fleming et al, 2022 )…”

Section: Introductionmentioning

confidence: 99%

Safeguarding Lysosomal Homeostasis by DNAJC5/CSPα-Mediated Unconventional Protein Secretion and Endosomal Microautophagy

2022

Front. Cell Dev. Biol.

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Neuronal ceroid lipofuscinosis (NCL) is a collection of genetically inherited neurological disorders characterized by vision loss, seizure, brain death, and premature lethality. At the cellular level, a key pathologic hallmark of NCL is the build-up of autofluorescent storage materials (AFSM) in lysosomes of both neurons and non-neuronal cells. Molecular dissection of the genetic lesions underlying NCLs has shed significant insights into how disruption of lysosomal homeostasis may lead to lipofuscin accumulation and NCLs. Intriguingly, recent studies on DNAJC5/CSPα, a membrane associated HSC70 co-chaperone, have unexpectedly linked lipofuscin accumulation to two intimately coupled protein quality control processes at endolysosomes. This review discusses how deregulation of unconventional protein secretion and endosomal microautophagy (eMI) contributes to lipofuscin accumulation and neurodegeneration.

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“…The link between RanBP2/Nup358 and mitochondrial function was further explored by Jomon Joseph (National centre for Cell Science, Pune, India). Impaired mitochondrial functions and autophagy have been implicated in many neurological disorders, possibly including ANE [ 107 , 108 ]. Joseph presented his lab work wherein he revealed that RanBP2/Nup358-positive annulate lamellae could often be present at ER-mitochondrial contact sites, which are hubs for regulation of various signaling pathways, intracellular calcium homeostasis, and autophagy [ 109 , 110 ].…”

Section: Ranbp2/nup358 In the Cytosolmentioning

confidence: 99%

Workshop on RanBP2/Nup358 and acute necrotizing encephalopathy

Palazzo

Joseph

Lim

et al. 2022

Nucleus

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Dominant missense mutations in RanBP2/Nup358 cause Acute Necrotizing Encephalopathy (ANE), a pediatric disease where seemingly healthy individuals develop a cytokine storm that is restricted to the central nervous system in response to viral infection. Untreated, this condition leads to seizures, coma, long-term neurological damage and a high rate of mortality. The exact mechanism by which RanBP2 mutations contribute to the development of ANE remains elusive. In November 2021, a number of clinicians and basic scientists presented their work on this disease and on the interactions between RanBP2/Nup358, viral infections, the innate immune response and other cellular processes.

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The different autophagy degradation pathways and neurodegeneration

Cited by 186 publications

References 332 publications

Urolithin A attenuates auditory cell senescence by activating mitophagy

Urolithin A attenuates auditory cell senescence by activating mitophagy

Safeguarding Lysosomal Homeostasis by DNAJC5/CSPα-Mediated Unconventional Protein Secretion and Endosomal Microautophagy

Workshop on RanBP2/Nup358 and acute necrotizing encephalopathy

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