Interactors and neighbors of ULK1 complex members DOI Creative Commons
Devanarayanan Siva Sankar, Jörn Dengjel

Autophagy, Год журнала: 2024, Номер unknown, С. 1 - 3

Опубликована: Окт. 12, 2024

The ULK1 kinase complex plays a crucial role in autophagosome biogenesis. To identify interactors or regulators of assembly influencing biogenesis, we performed an interaction proteomics screen. Employing both affinity purification and proximity labeling N- C-terminal tagged fusion proteins coupled to quantitative mass spectrometry, identified 317 high-confidence neighbors the four members, including member-specific common interactors. Interactions with selective macroautophagy/autophagy receptors indicate activation autophagy pathways by 90 min nutrient starvation. Focusing on effector protein BAG2, interactor approaches, highlight that phosphorylates supporting localization scaffold inducer AMBRA1 ER, thereby positively regulating initiation.

Язык: Английский

Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway DOI Creative Commons
Ying Zhao, Jia Li,

Anran Ma

и другие.

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Abstract Background: Disruption of hepatic lipid homeostasis leads to excessive triglyceride accumulation and the development metabolic dysfunction-associated steatotic liver disease (MASLD). Autophagy, a critical process in metabolism, is impaired MASLD pathogenesis. Irisin, skeletal muscle-driven myokine, regulates but its impact on metabolism not well understood. Here, we aimed explore role irisin steatosis underlying mechanisms involved. Methods: A high-fat diet (HFD)-induced mouse model was used, recombinant protein, herein referred as “Irisin”, intraperitoneally administered for 4 weeks evaluate effects accumulation. Liver tissues were stained with Oil red O (ORO), (TG) total cholesterol (TC) contents measured serum homogenates. The expression autophagosome marker microtubule-associated protein 1 light chain 3 (LC3), autophagy receptor sequestosome-1 (SQSTM1/p62), initiation complex unc-51-like kinase (ULK1) lysosomal functional cathepsin B via Western blotting, transcription factor EB (TFEB) analyzed immunofluorescence autophagic changes. effect flux further evaluated palmitic acid-induced HepG2 cells by measuring degradation chloroquine (CQ), analyzing colocalization LC3 lysosome-associated (LAMP1). possible mechanism examined sirtuin (SIRT3) pathway validated using overexpression SIRT3 plasmid transfection or siRNA-mediated knockdown. Student’s t -test utilized statistical analysis. Results: Irisin significantly reduces mice fed HFD, accompanied enhanced hepatocyte upregulation pathway. In cells, attenuated accumulation, which partially dependent levels. Mechanistically, treatment upregulated phosphorylated AMP-activated (AMPK), inhibited mammalian target rapamycin (mTOR) activity, promoted TFEB nucleus translocation, increased expression, degradation, alleviated steatosis. No significant changes phosphorylation ULK1 hepatocytes observed. However, when siRNA used knock down , those reversed, exacerbated. Conclusions: Our findings highlight potential therapeutic modulating potentially providing novel management MASLD. Further research needed elucidate clinical applications this approach

Язык: Английский

Процитировано

1

Mammalian nucleophagy: process and function DOI
Fujian Ji, Enyong Dai, Rui Kang

и другие.

Autophagy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 19, 2025

The nucleus is a highly specialized organelle that houses the cell's genetic material and regulates key cellular activities, including growth, metabolism, protein synthesis, cell division. Its structure function are tightly regulated by multiple mechanisms to ensure integrity genomic stability. Increasing evidence suggests nucleophagy, selective form of autophagy targets nuclear components, plays critical role in preserving clearing dysfunctional materials such as proteins (lamins, SIRT1, histones), DNA-protein crosslinks, micronuclei, chromatin fragments. Impaired nucleophagy has been implicated aging various pathological conditions, cancer, neurodegeneration, autoimmune disorders, neurological injury. In this review, we focus on mammalian cells, discussing its mechanisms, regulation, cargo selection, well evaluating therapeutic potential promoting human health mitigating disease.

Язык: Английский

Процитировано

0

Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy DOI Creative Commons
Alexandre Leytens, Rocío Benítez‐Fernández,

Carlos Jiménez-García

и другие.

Autophagy, Год журнала: 2024, Номер unknown, С. 1 - 16

Опубликована: Сен. 8, 2024

Macroautophagy/autophagy is a constitutively active catabolic lysosomal degradation pathway, often found dysregulated in human diseases. It considered to act cytoprotective manner and commonly upregulated cells undergoing stress. Its initiation regulated at the protein level does not require

Язык: Английский

Процитировано

0

Interactors and neighbors of ULK1 complex members DOI Creative Commons
Devanarayanan Siva Sankar, Jörn Dengjel

Autophagy, Год журнала: 2024, Номер unknown, С. 1 - 3

Опубликована: Окт. 12, 2024

The ULK1 kinase complex plays a crucial role in autophagosome biogenesis. To identify interactors or regulators of assembly influencing biogenesis, we performed an interaction proteomics screen. Employing both affinity purification and proximity labeling N- C-terminal tagged fusion proteins coupled to quantitative mass spectrometry, identified 317 high-confidence neighbors the four members, including member-specific common interactors. Interactions with selective macroautophagy/autophagy receptors indicate activation autophagy pathways by 90 min nutrient starvation. Focusing on effector protein BAG2, interactor approaches, highlight that phosphorylates supporting localization scaffold inducer AMBRA1 ER, thereby positively regulating initiation.

Язык: Английский

Процитировано

0