Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease DOI Creative Commons
Rohit A. Sinha

Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 39(5), P. 686 - 692

Published: Oct. 14, 2024

The influence of thyroid hormone (TH) on liver metabolism has attracted the attention pharmacologists seeking new treatments for metabolic dysfunction-associated steatotic disease (MASLD), an increasingly common disorder. In this context, selective induction autophagy by TH in preclinical models been identified as a promising mechanism. process, clears intrahepatic fat through lipophagy while protecting against inflammation and mitochondrial damage hepatocytes via mitophagy. Furthermore, TH-induced aggrephagy may represent protective mechanism to mitigate development MASLD-associated hepatocellular carcinoma. Considering defects observed during progression human MASLD, TH, its metabolites, analogs novel strategy combat hepatic across MASLD spectrum.

Language: Английский

Oxidative Stress and Cancer Therapy: Controlling Cancer Cells Using Reactive Oxygen Species DOI Open Access

Songhyun Ju,

Manish Kumar Singh,

Sunhee Han

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12387 - 12387

Published: Nov. 18, 2024

Cancer is a multifaceted disease influenced by various mechanisms, including the generation of reactive oxygen species (ROS), which have paradoxical role in both promoting cancer progression and serving as targets for therapeutic interventions. At low concentrations, ROS serve signaling agents that enhance cell proliferation, migration, resistance to drugs. However, at elevated levels, induce oxidative stress, causing damage biomolecules leading death. cells developed mechanisms manage activating pathways such NRF2, NF-κB, PI3K/Akt. This review explores relationship between cancer, focusing on death like apoptosis, ferroptosis, autophagy, highlighting potential strategies exploit target cells.

Language: Английский

Citations

15
Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion DOI Creative Commons
Luca Ferrari, Bernd Bauer, Y. Qiu

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(24)

Published: June 12, 2024

The accumulation of protein aggregates is a hallmark many diseases, including Alzheimer’s disease. As major pillar the proteostasis network, autophagy mediates degradation aggregates. cargo receptor p62 recognizes ubiquitin on proteins and cooperates with TAX1BP1 to recruit machinery. Paradoxically, are not degraded in various diseases despite association. Here, we reconstituted recognition by receptors physiological pathological Tau forms. Monomeric recruits via sequential actions chaperone ubiquitylation machineries. In contrast, fibrils from disease brains recognized but fail TAX1BP1. This failure due masking moieties p62. resistant deubiquitylation, and, thus, this nonproductive interaction irreversible. Our results shed light mechanism underlying evasion their consequent

Language: Английский

Citations

9
Phase separation of p62: roles and regulations in autophagy DOI
Xue Huang,

Jinpei Zhang,

Jia Yao

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62 DOI Creative Commons
Nikolas Furthmann, Verian Bader,

Lena Angersbach

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 19, 2023

Abstract NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of proteostasis by promoting autophagosomal clearance aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress are vulnerable to challenges. Moreover, patient with mutation the NEMO-encoding IKBKG gene resulting defective binding linear ubiquitin chains, developed widespread mixed brain proteinopathy, including α-synuclein, tau TDP-43 pathology. amplifies ubiquitylation at α-synuclein aggregates promotes local concentration p62 into foci. In vitro, lowers threshold concentrations required for ubiquitin-dependent phase transition p62. summary, reshapes aggregate surface efficient providing mobile interphase favoring co-condensation

Language: Английский

Citations

23
Transcription factor Nrf1 regulates proteotoxic stress-induced autophagy DOI Creative Commons
Madison A. Ward, Janakiram R. Vangala, Hatem Elif Kamber Kaya

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(6)

Published: April 24, 2024

Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates new synthesis, thus enabling cells mitigate stress. Here, we report that under similar circumstances, multiple components autophagy-lysosomal pathway (ALP) were transcriptionally upregulated an Nrf1-dependent fashion, providing with additional route cope insufficiency. In response inhibitors, Nrf1-deficient displayed profound defects invoking autophagy and clearance aggresomes. This phenomenon was also recapitulated NGLY1 knockout cells, where is known be non-functional. Conversely, overexpression induced ALP genes endowed increased capacity clear Overall, our results significantly expand shaping

Language: Английский

Citations

8
Amylin is incorporated into extracellular vesicles in an ESCRT-dependent manner and regulates senescence DOI

Sarai Iglesias-Fortes,

A. P. M. Lockwood,

Carlos González-Blanco

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167699 - 167699

Published: Jan. 1, 2025

Language: Английский

Citations

0
The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux DOI

Brian J. North,

Amelia E Ohnstad, Michael J. Ragusa

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(4)

Published: Jan. 8, 2025

During autophagy, toxic cargo is encapsulated by autophagosomes and trafficked to lysosomes for degradation. NBR1, an autophagy receptor targeting ubiquitinated aggregates, serves as a model studying the multivalent, heterotypic interactions of cargo-bound receptors. Here, we find that three critical NBR1 partners—ATG8-family proteins, FIP200, TAX1BP1—each bind distinct, overlapping determinants within short linear interaction motif (SLiM). To explore whether SLiMs extend beyond analyzed >100 LC3-interacting regions (LIRs), revealing FIP200 and/or TAX1BP1 binding LIRs common phenomenon suggesting protein hotspots. Phosphomimetic peptides demonstrate phosphorylation generally enhances ATG8-family but not TAX1BP1, indicating differential regulation. In vivo, LIR-mediated with promote optimal flux leveraging additional functionalities from TAX1BP1. These findings reveal one-to-many modality in LIR illustrating cooperative mechanisms receptors regulatory potential multifunctional SLiMs.

Language: Английский

Citations

0
Oxidized protein aggregate lipofuscin impairs cardiomyocyte contractility via late-stage autophagy inhibition DOI Creative Commons
Sophia Walter, Steffen P. Häseli, Peter Baumgarten

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103559 - 103559

Published: Feb. 19, 2025

Language: Английский

Citations

0
Autophagy, ER-phagy and ER dynamics during cell differentiation DOI Creative Commons
Michele Cillo,

Viviana Buonomo,

Anna Vainshtein

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169151 - 169151

Published: April 1, 2025

The endoplasmic reticulum (ER) is a multifunctional organelle essential for protein and lipid synthesis, ion transport inter-organelle communication. It comprises highly dynamic network of membranes that continuously reshape to support wide range cellular processes. During differentiation, extensive remodelling both ER architecture its proteome required accommodate alterations in cell morphology function. Autophagy, ER-phagy particular, plays pivotal role reshaping the ER, enabling cells meet their evolving needs adapt developmental cues. Despite ER's critical mechanisms responsible regulating dynamics are not fully understood. Emerging evidence suggests transcriptional post-translational regulation play fine-tuning unfolded response (UPR). This review explores molecular basis autophagy ER-phagy, highlighting during differentiation. A deeper understanding these processes could open new avenues targeted therapeutic approaches conditions where impaired.

Language: Английский

Citations

0
Autophagy-related lncRNAs and exosomal lncRNAs in colorectal cancer: focusing on lncRNA-targeted strategies DOI Creative Commons
Yan Dong, Yiwei He,

Y Geng

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Sept. 28, 2024

Autophagy is a cellular process that involves the degradation and recycling of components, including damaged proteins organelles. It an important mechanism for maintaining homeostasis has been implicated in various diseases, cancer. Long non-coding RNAs (lncRNAs) are class RNA molecules do not code but instead play regulatory roles gene expression. Emerging evidence suggests lncRNAs can influence autophagy contribute to development progression colorectal cancer (CRC). Several have identified as key players modulating CRC. The dysregulation (ncRNAs) CRC complex interplay between these two factors pathogenesis disease. Modulating may sensitize cells existing therapies or improve efficacy new treatment approaches. Additionally, targeting specific involved regulation could potentially be used therapeutic intervention inhibit tumor growth, metastasis, overcome drug resistance In this review, thorough overview presented, encompassing functions underlying mechanisms autophagy-related range critical areas within biology. These include cell proliferation, apoptosis, migration, invasion, resistance, angiogenesis, radiation resistance.

Language: Английский

Citations

3