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

High-intensity interval training alleviates exhaustive exercise-induced HSP70-assisted selective autophagy in skeletal muscle DOI Creative Commons
Jiao Lu, Liumei Zhang, Jingjing Liu

et al.

The Journal of Physiological Sciences, Journal Year: 2023, Volume and Issue: 73(1)

Published: Nov. 21, 2023

This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on maintenance proteostasis during exhaustive exercise and uncover alteration CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced adaptation response exercise. Rats were randomly divided into a control group; an HIIT + group. Results show myofibril damage BiP levels increased after exercise, HSP70, BAG3, ubiquitin, autophagy-related proteins, their interactions increased. intervention before could decrease injury levels, accompanied by down-regulation HSP70/BAG3 complex autophagy. In conclusion, promotes clear protein aggregation for keeping fibers; pre-HIIT improves unfold caused which might contribute inhibit augmentation CASA.

Language: Английский

Citations

3
Mechanism of TAX1BP1 recruitment in aggrephagy to switch from cargo collection to sequestration DOI Creative Commons
Bernd Bauer,

Jonas Idinger,

Martina Schuschnig

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 17, 2024

Abstract Autophagy mediates the degradation of harmful material within lysosomes. In aggrephagy, pathway mediating aggregated, ubiquitinated proteins, this cargo is collected in larger condensates prior to its sequestration by autophagosomes. process, SQSTM1/p62 and NBR1 drive condensation, while TAX1BP1, which binds recruits autophagy machinery facilitate autophagosome biogenesis at condensates. The mechanistic basis for TAX1BP1 mediated switch from collection unclear. Here we show that not a constitutive component Its recruitment correlates with induction biogenesis. sufficient recruit TBK1 kinase via SINTBAD adapter. We define - binding site, adjacent GABARAP/LC3 interaction site demonstrate mimetics can be enhanced an increased ubiquitin load. Our study suggests initiated once

Language: Английский

Citations

0
Proteomics Analysis of Proteotoxic Stress Response in In-Vitro Human Neuronal Models DOI Open Access

Ayodele Alaiya,

Bothina Mohammed Alharbi,

Zakia Shinwari

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6787 - 6787

Published: June 20, 2024

Heat stroke, a hazardous hyperthermia-related illness, is characterized by CNS injury, particularly long-lasting brain damage. A root cause for hyperthermic neurological damage heat-induced proteotoxic stress through protein aggregation, known causative agent of disorders. Stress magnitude and enduring persistence are highly correlated with hyperthermia-associated We used an untargeted proteomic approach using liquid chromatography–tandem mass spectrometry (LC-MS/MS) to identify characterize time-series proteome-wide changes in dose-responsive models medulloblastoma [Daoy], neuroblastoma [SH-SY5Y], differentiated SH-SY5Y neuron-like cells [SH(D)]. An integrated analysis condition–time datasets identified global differentially expressed proteins (DEPs) as part the response. The condition-specific detected higher DEPs upregulated extreme heat relatively conservative tight regulation cells. Functional network ingenuity pathway (IPA) common intercellular pathways associated biological processes protein, RNA, amino acid metabolism cellular response membrane trafficking. condition-wise temporal detects significant pathway, functional, disease association like folding synthesis, Nervous System Development Function, Neurological Disease. elaborate dose-dependent stress-specific neuroprotective signaling cascade also significantly activated. Thus, our study provides comprehensive map associating altered processes. This helps expand understanding molecular basis potential translational connotations.

Language: Английский

Citations

0
Quiescent cells maintain active degradation-mediated protein quality control requiring proteasome, autophagy and nucleus-vacuole junctions DOI

Dina Franić,

Mihaela Pravica,

Klara Zubčić

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 30, 2024

Abstract Many cells spend a major part of their life in quiescence, reversible state characterized by distinct cellular organization and metabolism. In glucose-depleted quiescent yeast cells, there is metabolic shift from glycolysis to mitochondrial respiration, large fraction proteasomes are reorganized into cytoplasmic granules containing disassembled particles. Given these changes, the operation protein quality control (PQC) particular reliance on degradation-mediated PQC specific pathways involved, remains unclear. By examining model misfolded proteins expressed we found that targeted for selective degradation requiring functional 26S proteasomes. This indicates significant pool active degrading substrates. Misfolded were degraded manner dependent E3 ubiquitin ligases Ubr1 San1, with playing dominant role. contrast exponentially growing efficient clearance certain additionally required intact nucleus-vacuole junctions (NVJ) Cue5-independent autophagy. Our findings suggest proteasome activity, autophagy, NVJ-dependent operate parallel. Together data demonstrate maintain relies primarily degradation. The necessity multiple removal during quiescence underscores importance this state.

Language: Английский

Citations

0
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

Citations

0