MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5

Nezich, Catherine L.; Wang, Chunxin; Fogel, Adam I.; Youle, Richard J.

doi:10.1084/jem.2129oia71

Cited by 26 publications

(42 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TFEB activation, translocation, and functional transactivation of needed target genes requires Parkin, ATG5, and ATG9, thus illustrating the interdependence between the early stages of phagophore construction (99, 100) and the projected transcriptional needs of mitophagy (8). Such interdependence is not seen when TFEB activation occurs after nutrient starvation, a stimulus that requires the biogenesis of autophagosomes and lysosomes to a lesser extent.…”

Section: Mit/tfe Transcription Factors Depend On Atg Functionsmentioning

confidence: 99%

“…TFEB and other MiT/TFE transcription factors are closely integrated with the process of autophagy (8). For mitophagy, a special form of autophagy modified for the lysosomal degradation of dysfunctional mitochondria, TFEB translocation into the nucleus requires the functions of both ATG5 and ATG9 (Fig.…”

Section: Mit/tfe Transcription Factors Depend On Atg Functionsmentioning

confidence: 99%

“…TFEB activation and translocation into the nucleus take place in a manner dependent on parkin, ATG5, and ATG9 and enables the successful transactivation of numerous lysosomal and autophagy genes. The role of ATG5 and ATG9 in contributing to the formation of the phagophore is the probable mechanism for their essential role in TFEB translocation into the nucleus, although some evidence suggests that both ATGs also enter into the nucleus (8). Glucose deprivation also stimulates TFEB activation and translocation but is not dependent on ATG5 and ATG9 dependence.…”

Section: Nrf2mentioning

confidence: 99%

“…However, because cell survival is constantly threatened by variations in both internal and external conditions, autophagy programs must be able to respond appropriately to stress. Stresses, such as nutrient or growth factor starvation, metabolic imbalance, hypoxia, oxidative stress, genotoxic stress, or unfolded protein stress all affect autophagy and induce adjustments, initially through posttranslational modifications of the autophagy-related (ATG) proteins but eventually of transcription factors, such as those in the p53, forkhead box O (FOXO), microphthalmia transcription factor (MiT/TFE), nuclear factor erythroid-derived 2-related factor 2 (Nrf2), and nuclear factor k-light chain enhancer of activated B cells (NFkB)/reticuloendotheliosis (Rel) families (2,(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Retrograde signaling from autophagy modulates stress responses

et al. 2017

View full text Add to dashboard Cite

Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for homeostasis and is constitutively functional in most cells, but it can also be implemented as part of stress responses. We discuss findings showing that autophagy proteins can modulate and amplify the activities of transcription factors involved in stress responses, such as those in the p53, FOXO, MiT/TFE, Nrf2, and NFkB/Rel families. Thus, transcription factors not only amplify stress responses and autophagy but are also subject to retrograde regulation by autophagy-related proteins. Physical interactions with autophagy-related proteins, competition for activating intermediates, and "signalphagy," which is the role autophagy plays in the degradation of specific signaling proteins, together provide powerful tools for implementing negative feedback or positive feed-forward loops on the transcription factors that regulate autophagy. We present examples illustrating how this network interacts to regulate metabolic and physiologic responses.

show abstract

Section: Mit/tfe Transcription Factors Depend On Atg Functionsmentioning

confidence: 99%

Section: Mit/tfe Transcription Factors Depend On Atg Functionsmentioning

confidence: 99%

Section: Nrf2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Retrograde signaling from autophagy modulates stress responses

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In particular, TFEB has been shown to bind to the promoter regions of numerous autophagy genes and to induce autophagosome biogenesis and autophagosome-lysosome fusion (Settembre et al, 2011). Interestingly, TFEB overexpression results in the enhanced degradation of bulk autophagy substrates such as long-lived proteins (Settembre et al, 2011), as well as in the clearance of lipid droplets and damaged mitochondria (Nezich et al, 2015;Settembre et al, 2013a), indicating that this transcription factor also plays a role in modulating organelle-specific autophagy, such as lipophagy and mitophagy. TFEB has also been found to induce lysosomal exocytosis , a process by which lysosomes fuse to the plasma membrane and secrete their content to the extracellular space.…”

Section: Tfeb As a Master Regulator Of Lysosomal Function And Autophagymentioning

confidence: 99%

TFEB at a glance

Napolitano

Ballabio

2016

Journal of Cell Science

585

637

View full text Add to dashboard Cite

The transcription factor EB (TFEB) plays a pivotal role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation, which occurs at the lysosomal surface. Phosphorylated TFEB is retained in the cytoplasm, whereas dephosphorylated TFEB translocates to the nucleus to induce the transcription of target genes. Thus, a lysosome-to-nucleus signaling pathway regulates cellular energy metabolism through TFEB. Recently, in vivo studies have revealed that TFEB is also involved in physiological processes, such as lipid catabolism. TFEB has attracted a lot of attention owing to its ability to induce the intracellular clearance of pathogenic factors in a variety of murine models of disease, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity. In this Cell Science at a Glance article and accompanying poster, we present an overview of the latest research on TFEB function and its implication in human diseases.

show abstract

The lysosomal membrane protein LAMP‐2 is dispensable for PINK1/Parkin‐mediated mitophagy

et al. 2019

View full text Add to dashboard Cite

Selective autophagy for the elimination of aberrant mitochondria, termed mitophagy, can be regulated by the kinase PINK1 and the ubiquitin ligase Parkin. The lysosome‐associated membrane protein 2 (LAMP‐2) plays diverse functions in non‐selective autophagy, chaperone‐mediated autophagy and selective autophagy for the degradation of RNA/DNA. In the present study, we investigated whether LAMP‐2 plays important roles during PINK1/Parkin‐mediated mitophagy. The results obtained clearly show that knockdown of LAMP‐2 does not cause defects in mitophagy in HeLa cells stably expressing Parkin, indicating that LAMP‐2 is dispensable for PINK1/Parkin‐mediated mitophagy. The present study is the first to determine the potential role of LAMP‐2 in PINK1/Parkin‐mediated mitophagy, thereby providing more insight into the sophisticated process of mitophagy.

show abstract

MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5

Cited by 26 publications

References 30 publications

Retrograde signaling from autophagy modulates stress responses

Retrograde signaling from autophagy modulates stress responses

TFEB at a glance

The lysosomal membrane protein LAMP‐2 is dispensable for PINK1/Parkin‐mediated mitophagy

Contact Info

Product

Resources

About