Action and therapeutic targets of folliculin interacting protein 1: a novel signaling mechanism in redox regulation DOI Creative Commons

Qingzhi Ran,

Aoshuang Li,

Bo Yao

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 12, 2025

Rapid activation of adenosine monophosphate-activated protein kinase (AMPK) induces phosphorylation mitochondrial-associated proteins, a process by which phosphate groups are added to regulate mitochondrial function, thereby modulating energy metabolism, triggering an acute metabolic response, and sustaining adaptation through transcriptional regulation. AMPK directly phosphorylates folliculin interacting 1 (FNIP1), leading the nuclear translocation transcription factor EB (TFEB) in response functions. While function is tightly linked finely-tuned energy-sensing mobility, FNIP1 plays critical roles glucose transport sensing, autophagy, cellular stress muscle fiber contraction. Consequently, emerges as promising novel target for addressing aberrant metabolism. Recent evidence indicates that implicated biology various pathways, including AMPK, mTOR, ubiquitination, oxidative responses, skeletal Nonetheless, there dearth literature discussing physiological mechanism action therapeutic target. This review outlines how regulates metabolic-related signaling pathways enzyme activities, such catalytic activity enzymes, homeostasis products, controlling fate different contexts. Our focus will be on elucidating these metabolite-mediated processes inflammatory diseases.

Язык: Английский

Stress granules plug and stabilize damaged endolysosomal membranes DOI Creative Commons
Claudio Bussi, Agustín Mangiarotti, Christian Vanhille-Campos

и другие.

Nature, Год журнала: 2023, Номер 623(7989), С. 1062 - 1069

Опубликована: Ноя. 15, 2023

Abstract Endomembrane damage represents a form of stress that is detrimental for eukaryotic cells 1,2 . To cope with this threat, possess mechanisms repair the and restore cellular homeostasis 3–7 also results in organelle instability by which stabilize damaged endomembranes to enable membrane remains unknown. Here, combining vitro cellulo studies computational modelling we uncover biological function granules whereby these biomolecular condensates rapidly at endomembrane sites act as plug stabilizes ruptured membrane. Functionally, demonstrate granule formation stabilization efficient endolysosomes, through both ESCRT (endosomal sorting complex required transport)-dependent independent mechanisms. We show blocking human macrophages creates permissive environment Mycobacterium tuberculosis , pathogen exploits survive within host.

Язык: Английский

Процитировано

55
Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy DOI Creative Commons
Jake Cross, Joanne Durgan, David G. McEwan

и другие.

The Journal of Cell Biology, Год журнала: 2023, Номер 222(12)

Опубликована: Сен. 8, 2023

Cells harness multiple pathways to maintain lysosome integrity, a central homeostatic process. Damaged lysosomes can be repaired or targeted for degradation by lysophagy, selective autophagy process involving ATG8/LC3. Here, we describe parallel ATG8/LC3 response damage, mechanistically distinct from lysophagy. Using comprehensive series of biochemical, pharmacological, and genetic approaches, show that damage induces non-canonical Conjugation ATG8s Single Membranes (CASM). Following are rapidly directly conjugated onto membranes, independently ATG13/WIPI2, lipidating PS (and PE), molecular hallmark CASM. Lysosome drives V-ATPase V0-V1 association, direct recruitment ATG16L1 via its WD40-domain/K490A, is sensitive Salmonella SopF. damage-induced CASM associated with formation dynamic, LC3A-positive tubules, promotes robust LC3A engagement ATG2, lipid transfer protein repair. Together, our data identify ATG8 conjugation as rapid important links dynamics.

Язык: Английский

Процитировано

53
Atg8 family proteins, LIR/AIM motifs and other interaction modes DOI Creative Commons
Vladimir V. Rogov, Ioannis P. Nezis,

Panagiotis Tsapras

и другие.

Autophagy Reports, Год журнала: 2023, Номер 2(1)

Опубликована: Март 19, 2023

The Atg8 family of ubiquitin-like proteins play pivotal roles in autophagy and other processes involving vesicle fusion transport where the lysosome/vacuole is end station. Nuclear are also emerging. Here, we review structural functional features their protein-protein interaction modes model organisms such as yeast, Arabidopsis, C. elegans Drosophila to humans. Although varying number homologs, from one yeast seven humans, more than ten some plants, there a strong evolutionary conservation modes. most prominent mode between LC3 interacting region (LIR), called motif (AIM), binding LIR docking site (LDS) homologs. There variants these motifs like "half-LIRs" helical LIRs. We discuss details how selectivity achieved well role multivalent LIR-LDS interactions selective autophagy. A known be regulated by phosphorylation. New methods predict have emerged that will aid discovery analyses. surfaces LDS becoming presently lack detailed information, N-terminal arm UIM-docking (UDS). More likely discovered future studies.

Язык: Английский

Процитировано

51
Membrane atg8ylation in Canonical and Noncanonical Autophagy DOI
Vojo Deretić, Thabata Duque, Einar S Trosdal

и другие.

Journal of Molecular Biology, Год журнала: 2024, Номер 436(15), С. 168532 - 168532

Опубликована: Март 12, 2024

Язык: Английский

Процитировано

17
Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function DOI Creative Commons

Masroor Ahmad Paddar,

Fulong Wang, Einar S Trosdal

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Янв. 7, 2025

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number biological outputs includes control tuberculosis in animal models. Here, we show that associates retromer’s components VPS26, VPS29, and VPS35 modulates retromer function. Knockout blocked trafficking key glucose transporter sorted by retromer, GLUT1, to plasma membrane. Knockouts other genes essential for component, affected GLUT1 sorting, indicating atg8ylation process affects function endosomal sorting. The contribution sorting was independent canonical autophagy. These findings expand scope specific processes cell dependent on its known interactors.

Язык: Английский

Процитировано

2
TECPR1 is activated by damage‐induced sphingomyelin exposure to mediate noncanonical autophagy DOI Creative Commons
Namrita Kaur, Laura Rodríguez de la Ballina, Håvard Styrkestad Haukaas

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(17)

Опубликована: Июль 6, 2023

Cells use noncanonical autophagy, also called conjugation of ATG8 to single membranes (CASM), label damaged intracellular compartments with ubiquitin-like family proteins in order signal danger caused by pathogens or toxic compounds. CASM relies on E3 complexes sense membrane damage, but so far, only the mechanism activate ATG16L1-containing complexes, associated proton gradient loss, has been described. Here, we show that TECPR1-containing are key mediators cells treated a variety pharmacological drugs, including clinically relevant nanoparticles, transfection reagents, antihistamines, lysosomotropic compounds, and detergents. Interestingly, TECPR1 retains activity when ATG16L1 is obstructed Salmonella Typhimurium pathogenicity factor SopF. Mechanistically, recruited damage-induced sphingomyelin (SM) exposure using two DysF domains, resulting its activation lipidation. In vitro assays purified human TECPR1-ATG5-ATG12 complex direct SM, whereas SM no effect ATG16L1-ATG5-ATG12. We conclude activator downstream exposure.

Язык: Английский

Процитировано

38
An ATG12‐ATG5‐TECPR1 E3‐like complex regulates unconventional LC3 lipidation at damaged lysosomes DOI Creative Commons
Dale Corkery, Sergio Castro‐Gonzalez, Anastasia Knyazeva

и другие.

EMBO Reports, Год журнала: 2023, Номер 24(9)

Опубликована: Июнь 29, 2023

Abstract Lysosomal membrane damage represents a threat to cell viability. As such, cells have evolved sophisticated mechanisms maintain lysosomal integrity. Small lesions are detected and repaired by the endosomal sorting complex required for transport (ESCRT) machinery while more extensively damaged lysosomes cleared galectin‐dependent selective macroautophagic pathway (lysophagy). In this study, we identify novel role autophagosome‐lysosome tethering factor, TECPR1, in repair. promotes TECPR1 recruitment membranes via its N‐terminal dysferlin domain. This occurs upstream of galectin precedes induction lysophagy. At membrane, forms an alternative E3‐like conjugation with ATG12‐ATG5 conjugate regulate ATG16L1‐independent unconventional LC3 lipidation. Abolishment lipidation ATG16L1/TECPR1 double knockout impairs recovery following damage.

Язык: Английский

Процитировано

36
ATG5 provides host protection acting as a switch in the atg8ylation cascade between autophagy and secretion DOI Creative Commons
Fulong Wang,

Ryan Peters,

Jingyue Jia

и другие.

Developmental Cell, Год журнала: 2023, Номер 58(10), С. 866 - 884.e8

Опубликована: Апрель 12, 2023

Язык: Английский

Процитировано

34
Mammalian ATG8 proteins maintain autophagosomal membrane integrity through ESCRTs DOI
Ruheena Javed, Ashish Jain, Thabata Duque

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(14)

Опубликована: Июнь 5, 2023

Язык: Английский

Процитировано

29
PRKAA2, MTOR, and TFEB in the regulation of lysosomal damage response and autophagy DOI
Mohd Shariq, Mohammad Firoz Khan, Reshmi Raj

и другие.

Journal of Molecular Medicine, Год журнала: 2024, Номер 102(3), С. 287 - 311

Опубликована: Янв. 6, 2024

Язык: Английский

Процитировано

12