Mechanisms of mitochondrial reorganization DOI Open Access

Tatsuro Maruyama,

Yutaro Hama, Nobuo N. Noda

и другие.

The Journal of Biochemistry, Год журнала: 2023, Номер 175(2), С. 167 - 178

Опубликована: Ноя. 28, 2023

Abstract The cytoplasm of eukaryotes is dynamically zoned by membrane-bound and membraneless organelles. Cytoplasmic zoning allows various biochemical reactions to take place at the right time place. Mitochondrion a organelle that provides zone for intracellular energy production metabolism lipids iron. A key feature mitochondria their high dynamics: constantly undergo fusion fission, excess or damaged are selectively eliminated mitophagy. Therefore, appropriate model systems understand dynamic cytoplasmic membrane In this review, we summarize molecular mechanisms mitochondrial fission as well mitophagy unveiled through studies using yeast mammalian models.

Язык: Английский

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

Xijing Yuan

и другие.

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 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

Язык: Английский

Процитировано

2
Nix interacts with WIPI2 to induce mitophagy DOI Creative Commons
Eric Bunker, François Le Guerroué, Chunxin Wang

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(22)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

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

Lixiu Ma,

Tianyu Han,

Y M Zhan

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 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

Язык: Английский

Процитировано

12
Physiological functions of ULK1/2 DOI Creative Commons
Gautam Pareek,

Mondira Kundu

Journal of Molecular Biology, Год журнала: 2024, Номер 436(15), С. 168472 - 168472

Опубликована: Фев. 2, 2024

UNC-51-like kinases 1 and 2 (ULK1/2) are serine/threonine that best known for their evolutionarily conserved role in the autophagy pathway. Upon sensing nutrient status of a cell, ULK1/2 integrate signals from upstream cellular energy sensors such as mTOR AMPK relay them to downstream components machinery. also play indispensable roles selective pathway, removing damaged mitochondria, invading pathogens, toxic protein aggregates. Additional functions have emerged beyond autophagy, including trafficking, RNP granule dynamics, signaling events impacting innate immunity, axon guidance, homeostasis, cell fate. Therefore, it is no surprise alterations expression activity been linked with pathophysiological processes, cancer, neurological disorders, cardiovascular diseases. Growing evidence suggests function biological rheostats, tuning intra extra-cellular cues. Given broad physiological relevance, candidate targets small molecule activators or inhibitors may pave way development therapeutics treatment diseases humans.

Язык: Английский

Процитировано

9
The NRF2 activator RTA-408 ameliorates chronic alcohol exposure-induced cognitive impairment and NLRP3 inflammasome activation by modulating impaired mitophagy initiation DOI
Xinrou Lin, Hongxuan Wang,

Lubin Zou

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 220, С. 15 - 27

Опубликована: Апрель 27, 2024

Язык: Английский

Процитировано

9
Reconstitution of BNIP3/NIX-mediated autophagy reveals two pathways and hierarchical flexibility of the initiation machinery DOI Creative Commons
Elias Adriaenssens, Stefan Schaar, Annan SI Cook

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Selective autophagy is a lysosomal degradation pathway that critical for maintaining cellular homeostasis by disposing of harmful material. While the mechanisms which soluble cargo receptors recruit machinery are becoming increasingly clear, principles governing how organelle-localized transmembrane initiate selective remain poorly understood. Here, we demonstrate can autophagosome biogenesis not only recruiting upstream FIP200/ULK1 complex but also via WIPI-ATG13 complex. This latter employed BNIP3/NIX to trigger mitophagy. Additionally, other mitophagy receptors, including FUNDC1 and BCL2L13, exclusively use complex, while FKBP8 ER-phagy receptor TEX264 capable utilizing both pathways autophagy. Our study defines molecular rules initiation revealing remarkable flexibility in assembly activation machinery, with significant implications therapeutic interventions.

Язык: Английский

Процитировано

9
Diverse routes to mitophagy governed by ubiquitylation and mitochondrial import DOI Creative Commons
Michael J. Clague, Sylvie Urbé

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

HighlightsStructural and biochemical studies of PINK1 activation stabilisation have captured TOM complex interactions the formation a PINK1–TOM–TIM supercomplex.USP30 inhibition shows promising preclinical indications.FBXL4 is major suppressor NIX/BNIP3-dependent mitophagy.PPTC7 scaffolds interaction FBXL4–SCF ligase with BNIP3 NIX.Control PPTC7 mitochondrial import sets levels NIX.AbstractThe selective removal mitochondria by mitophagy proceeds via multiple mechanisms essential for human well-being. The PINK1/Parkin NIX/BNIP3 pathways are strongly linked to dysfunction hypoxia, respectively. Both regulated ubiquitylation import. Recent elucidated how ubiquitin kinase acts as sensor stress through stable supercomplex. stability NIX SCFFBXL4 complex. Substrate recognition requires an adaptor molecule, PPTC7, whose availability limited Unravelling functional implications each mode remains critical challenge. We propose that prompts switch between these two pathways.

Язык: Английский

Процитировано

1
Natural compounds modulating mitophagy: Implications for cancer therapy DOI

Min Cao,

Yancheng Tang,

Yufei Luo

и другие.

Cancer Letters, Год журнала: 2023, Номер 582, С. 216590 - 216590

Опубликована: Дек. 12, 2023

Язык: Английский

Процитировано

18
The interplay between autophagy and cGAS-STING signaling and its implications for cancer DOI Creative Commons
Maximilian Schmid, Patrick D. Fischer, Magdalena Engl

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 10, 2024

Autophagy is an intracellular process that targets various cargos for degradation, including members of the cGAS-STING signaling cascade. senses cytosolic double-stranded DNA and triggers innate immune response through type I interferons. Emerging evidence suggests autophagy plays a crucial role in regulating fine-tuning signaling. Reciprocally, pathway can actively induce canonical as well non-canonical forms autophagy, establishing regulatory network feedback mechanisms alter both autophagic pathway. The crosstalk between impacts wide variety cellular processes such protection against pathogenic infections neurodegenerative disease, autoinflammatory disease cancer. Here we provide comprehensive overview involved signaling, with specific focus on interactions two pathways their importance

Язык: Английский

Процитировано

7
TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery DOI Creative Commons
Bhaskar Saha, Hallvard Lauritz Olsvik,

Geneva L. Williams

и другие.

Cell Reports, Год журнала: 2024, Номер 43(6), С. 114294 - 114294

Опубликована: Май 29, 2024

Ubiquitination of mitochondrial proteins provides a basis for the downstream recruitment mitophagy machinery, yet whether ubiquitination machinery itself contributes to is unknown. Here, we show that K63-linked polyubiquitination key regulator TBK1 essential its functions. This modification catalyzed by ubiquitin ligase TRIM5α and required interact with activate set ubiquitin-binding autophagy adaptors including NDP52, p62/SQSTM1, NBR1. Autophagy adaptors, along TRIM27, enable engage following damage. TRIM5α's activity accumulation active on damaged mitochondria in Parkin-dependent Parkin-independent pathways. Our data support model which mitochondria-localized, ubiquitin-based, self-amplifying assembly platform ultimately necessary core machinery.

Язык: Английский

Процитировано

5