Ion channels in the regulation of autophagy

Kondratskyi, Artem; Kondratska, Kateryna; Skryma, Roman; Klionsky, Daniel J.; Prevarskaya, Natalia

doi:10.1080/15548627.2017.1384887

Cited by 86 publications

(75 citation statements)

References 207 publications

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“…In general, this Ca 2+ signaling is due to differential localization near the PM or organelles, such as the endoplasmatic reticulum (ER), mitochondria, lysosomes, Golgi, and nucleus, with different mechanisms of activation and regulation . In a healthy cellular state, a spontaneous, basal inositol trisphosphate receptor (IP3R)‐mediated Ca 2+ signal occurs from the ER to the mitochondria in order to promote mitochondrial bioenergetics and ATP production .…”

Section: Molecular Regulation Of Autophagy Machinerymentioning

confidence: 99%

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Al‐Bari

2020

Annals of the New York Academy of Sciences

196

109

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Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy‐related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR‐independent signaling pathways. Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health.

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Section: Molecular Regulation Of Autophagy Machinerymentioning

confidence: 99%

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Al‐Bari

2020

Annals of the New York Academy of Sciences

196

109

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“…Because EFs essentially represent changes in the status, and the flux of ions is the essence of EFs, they inevitably induce changes in extracellular and cytoplasmic ion concentrations and ion channels activity. Recently, calcium-, chloride-and sodium-permeable ion channels have been found to regulate both basal and induced autophagy (51,52). Thus, we reasoned that EF-induced autophagy may be mediated by ion channels.…”

Section: Discussionmentioning

confidence: 95%

Autophagy is required for the directed motility of keratinocytes driven by electric fields

Yan

Jiang

Lin³

et al. 2018

FASEB j.

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Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF‐biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration. Initially, we found that electrical signals directed keratinocytes to the cathode with enhanced motility parameters [i.e., trajectory distance, trajectory speed, displacement distance, and displacement speed (Td/t)] and more efficient migration (directionality and Td/t along the x axis, among others). Meanwhile, EFs induced a time‐dependent increase in autophagic activity in keratinocytes, with constant autophagic flux, accompanied by increased transcription of numerous autophagy‐related genes. Deficiency in Atg5, a key protein necessary for autophagosome formation, led to significant reduction of autophagy, which was accompanied by a substantial reduction in EF‐stimulated directed motility. These results demonstrated a causal relationship between autophagy and EF‐directed migratory speed. In addition, both cell migration under normal conditions and EF‐biased directionality were autophagy independent. Thus, our findings define autophagy as an important functional regulator of electrically enhanced directed motility, adding to a growing understanding of EFs.—Yan, T., Jiang, X., Lin, G., Tang, D., Zhang, J., Guo, X., Zhang, D., Zhang, Q., Jia, J., Huang, Y. Autophagy is required for the directed motility of keratinocytes driven by electric fields. FASEB J. 33, 3922–3935 (2019). http://www.fasebj.org

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“…LC3‐I, the soluble type of autophagy, involved in the elongation via lipid conjugation to converse to LC3‐II, the vesicle‐affined form, which is generally supposed to be a specific marker protein of autophagy . The LC3‐II form is involved during the late steps of autophagy after the isolation membrane has formed . Sequestosome 1, commonly known as p62/SQSTM1, which is an ubiquitin‐combined scaffold protein, combining to LC3 using a designated sequence and serving as a specific substrate for autophagic flux via linking ubiquitin‐like proteins to the autophagic‐related proteins to accomplish degradation in the lysosome .…”

Section: Discussionmentioning

confidence: 99%

“…8 The LC3-II form is involved during the late steps of autophagy after the isolation membrane has formed. 60 Sequestosome 1, commonly known as p62/SQSTM1, which is an ubiquitin-combined scaffold protein, combining to LC3 using a designated sequence and serving as a specific substrate for autophagic flux via linking ubiquitin-like proteins to the autophagic-related proteins to accomplish degradation in the lysosome. 61 Beclin-1 is an essential component of the vacuolar protein sorting 34 (Vps34) complexes that upregulate autophagy.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic effects of rhein through the mitochondrial pathways, two death receptor pathways, and reducing autophagy in human liver L02 cells

Shen

Bao

et al. 2019

Environmental Toxicology

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Rhein (4,5‐dihydroxyanthraquinone‐2‐carboxylic acid) is a major component of many medicinal herbs such as Rheum palmatum L. and Polygonum multiflorum. Despite being widely used, intoxication cases associated with rhein‐containing herbs are often reported. Currently, there are no available reports addressing the effects of rhein on apoptosis in human liver L02 cells. Thus, the aim of this study is to determine the cytotoxic effects and the underlying mechanism of rhein on human normal liver L02 cells. In the present study, the methyl thiazolyl tetrazolium assay demonstrated that rhein decreased the viability of L02 cells in dose‐dependent and time‐dependent ways. Rhein was found to trigger apoptosis in L02 cells as shown by Annexin V‐fluoresceine isothiocyanate (FITC) apoptosis detection kit and cell mitochondrial membrane potential (MMP) assay, with nuclear morphological changes demonstrated by Hoechst 33258 staining. Detection of intracellular superoxide dismutase activity, lipid oxidation (malondialdehyde) content, and reactive oxygen species (ROS) levels showed that apoptosis was associated with oxidative stress. Moreover, it was observed that the mechanism implicated in rhein‐induced apoptosis was presumably via the death receptor pathway and the mitochondrial pathway, as illustrated by upregulation of TNF‐α, TNFR1, TRADD, and cleaved caspase‐3, and downregulation of procaspase‐8, and it is suggested that rhein may increase hepatocyte apoptosis by activating the increase of TNF‐α level. Meanwhile, rhein upregulates the expression of Bax and downregulates the expression of procaspase‐9 and ‐3, and it is suggested that the mitochondrial pathway is activated and rhein‐induced apoptosis may be involved. In addition, we also want to explore whether rhein‐induced apoptosis is related to the autophagic changes induced by rhein. The results showed that rhein treatment increased P62 and decreased LC3‐II and beclin‐1, which means that autophagy was weakened. The results of our studies indicated that rhein induced caspase‐dependent apoptosis via both the Fas death pathway and the mitochondrial pathway by generating ROS, and meanwhile the autophagy tended to weaken.

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Ion channels in the regulation of autophagy

Cited by 86 publications

References 207 publications

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Autophagy is required for the directed motility of keratinocytes driven by electric fields

Apoptotic effects of rhein through the mitochondrial pathways, two death receptor pathways, and reducing autophagy in human liver L02 cells

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