Autophagy in tumor immune escape and immunotherapy DOI Creative Commons
Huan Wang, Peng Sun,

Xijing Yuan

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 19, 2025

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of resistance remains significant. Autophagy, cellular response to various stressors, involves degradation damaged proteins and organelles via lysosomal pathways, maintaining homeostasis. This process not only supports cell survival but also profoundly impacts efficacy cancer immunotherapies. modulation autophagy cells or exerts dual effects on immunotherapy. However, mechanistic details how influences system therapy remain inadequately understood. Given this complexity, deeper understanding role tumor-immune landscape could reveal novel therapeutic avenues. By manipulating appropriately, it may be possible overcome enhance effectiveness immunotherapeutic strategies. article summarizes immunity, its relationship with immunotherapy, potential benefits strengthen antitumor responses optimize outcomes

Language: Английский

The role of PINK1–Parkin in mitochondrial quality control DOI
Derek P. Narendra, Richard J. Youle

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(10), P. 1639 - 1651

Published: Oct. 1, 2024

Language: Английский

Citations

42
Optineurin provides a mitophagy contact site for TBK1 activation DOI Creative Commons
Koji Yamano,

Momoha Sawada,

Reika Kikuchi

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(5), P. 754 - 779

Published: Jan. 29, 2024

Abstract Tank-binding kinase 1 (TBK1) is a Ser/Thr that involved in many intracellular processes, such as innate immunity, cell cycle, and apoptosis. TBK1 also important for phosphorylating the autophagy adaptors mediate selective autophagic removal of damaged mitochondria. However, mechanism by which PINK1-Parkin-mediated mitophagy activates remains largely unknown. Here, we show adaptor optineurin (OPTN) provides unique platform activation. Both OPTN-ubiquitin OPTN-pre-autophagosomal structure (PAS) interaction axes facilitate assembly OPTN-TBK1 complex at contact sites between mitochondria autophagosome formation sites. At this point, positive feedback loop activation initiated accelerates hetero-autophosphorylation protein. Expression monobodies engineered here to bind OPTN impaired accumulation sites, well subsequent TBK1, thereby inhibiting mitochondrial degradation. Taken together, these data reciprocal relationship initiates biogenesis on

Language: Английский

Citations

26
Targeting mitophagy in neurodegenerative diseases DOI
Odetta Antico, Paul Thompson, Nicholas T. Hertz

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

Citations

8
Mitophagy in the retina: Viewing mitochondrial homeostasis through a new lens DOI Creative Commons
Juan Ignacio Jiménez‐Loygorri, Rocío Benítez‐Fernández, Álvaro Viedma-Poyatos

et al.

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 96, P. 101205 - 101205

Published: July 15, 2023

Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of highest metabolic rates body-wide constantly exposed photooxidative damage external stressors. Mitophagy selective autophagic degradation mitochondria within lysosomes, can be triggered by distinct stimuli such as mitochondrial or hypoxia. Here, we review importance mitophagy retinal physiology pathology. In developing essential for reprogramming differentiation retina ganglion cells (RGCs). basal conditions, acts a quality control mechanism, maintaining healthy pool meet cellular demands. We summarize different autophagy- mitophagy-deficient mouse models described literature, discuss potential role dysregulation diseases glaucoma, diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration. Finally, provide overview methods used monitor vitro, ex vivo, vivo. This highlights important sustaining visual function, its putative therapeutic target other diseases.

Language: Английский

Citations

31
Nix interacts with WIPI2 to induce mitophagy DOI Creative Commons
Eric Bunker, François Le Guerroué, Chunxin Wang

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(22)

Published: Aug. 25, 2023

Nix is a membrane-anchored outer mitochondrial protein that induces mitophagy. While has an LC3-interacting (LIR) motif binds to ATG8 proteins, it also contains minimal essential region (MER) mitophagy through unknown mechanism. We used chemically induced dimerization (CID) probe the mechanism of Nix-mediated and found both LIR MER are required for robust find interacts with autophagy effector WIPI2 recruits mitochondria. The converts homogeneous distribution on surface mitochondria into puncta, even in absence ATG8s. Together, this work reveals unanticipated mechanisms Nix-induced elusive role MER, while describing interesting example induction acts downstream canonical initiation complexes.

Language: Английский

Citations

23
Mechanism and role of mitophagy in the development of severe infection DOI Creative Commons

Lixiu Ma,

Tianyu Han,

Y M Zhan

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 19, 2024

Abstract Mitochondria produce adenosine triphosphate and potentially contribute to proinflammatory responses cell death. Mitophagy, as a conservative phenomenon, scavenges waste mitochondria their components in the cell. Recent studies suggest that severe infections develop alongside mitochondrial dysfunction mitophagy abnormalities. Restoring protects against excessive inflammation multiple organ failure sepsis. Here, we review normal process, its interaction with invading microorganisms immune system, summarize mechanism of during infection. We highlight critical role preventing

Language: Английский

Citations

12
A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy DOI Creative Commons
Dan Tudorica, Bishal Basak,

Alexia S. Puerta Cordova

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(7)

Published: April 6, 2024

Activation of PINK1 and Parkin in response to mitochondrial damage initiates a that includes phosphorylation RAB7A at Ser72. Rubicon is binding negative regulator autophagy. The structure the Rubicon:RAB7A complex suggests Ser72 would block binding. Indeed, vitro by TBK1 abrogates Pacer, positive autophagy, has an RH domain with basic triad predicted bind introduced phosphate. Consistent this, Pacer-RH binds phosho-RAB7A but not unphosphorylated RAB7A. In cells, depolarization reduces colocalization whilst recruiting Pacer phospho-RAB7A–positive puncta. knockout mitophagy little effect on bulk autophagy or Parkin-independent mitophagy. Rescue Parkin-dependent requires intact pRAB7A phosphate-binding Pacer. Together these structural functional data support model which TBK1-dependent serves as switch, promoting relieving inhibition favoring activation.

Language: Английский

Citations

11
Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD DOI Creative Commons
Elias Adriaenssens, Thanh Ngoc Nguyen, Justyna Sawa‐Makarska

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(11), P. 1717 - 1731

Published: June 25, 2024

Abstract Mitophagy preserves overall mitochondrial fitness by selectively targeting damaged mitochondria for degradation. The regulatory mechanisms that prevent PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin (PINK1/Parkin)-dependent mitophagy other selective autophagy pathways from overreacting while ensuring swift progression once initiated are largely elusive. Here, we demonstrate how the TBK1 (TANK-binding 1) adaptors NAP1 (NAK-associated protein SINTBAD (similar to adaptor) restrict initiation of OPTN (optineurin)-driven competing with TBK1. Conversely, they promote nuclear dot 52 (NDP52)-driven recruiting NDP52 stabilizing its interaction FIP200. Notably, emerges as primary recruiter during initiation, which in return boosts NDP52-mediated mitophagy. Our results thus define cargo receptor rheostats, elevating threshold promoting pathway set motion supporting NDP52. These findings shed light on cellular strategy hyperactivity still efficient progression.

Language: Английский

Citations

10
Spautin-1 promotes PINK1-PRKN-dependent mitophagy and improves associative learning capability in an alzheimer disease animal model DOI Creative Commons
Juan Yi, Heling Wang, Guang Lu

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(12), P. 2655 - 2676

Published: July 25, 2024

Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 promoting degradation of PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy form for removal damaged superfluous mitochondria autophagy-lysosome pathway. Here, we report surprising discovery that, spautin-1 as an effective inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, facilitates stabilization activation full-length PINK1 at outer membrane (OMM) binding to components TOMM complex (TOMM70 TOMM20), leading disruption import prevention PARL-mediated cleavage. Moreover, induces neuronal in

Language: Английский

Citations

10
Response to Bruton’s tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy DOI
James D. Phelan, Sebastian Scheich, Jaewoo Choi

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 238 - 252.e9

Published: Jan. 11, 2024

Language: Английский

Citations

9