Mechanisms of mitochondrial reorganization DOI Open Access

Tatsuro Maruyama,

Yutaro Hama, Nobuo N. Noda

et al.

The Journal of Biochemistry, Journal Year: 2023, Volume and Issue: 175(2), P. 167 - 178

Published: Nov. 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.

Language: Английский

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

Mondira Kundu

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(15), P. 168472 - 168472

Published: Feb. 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.

Language: Английский

Citations

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

et al.

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

Published: Aug. 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.

Language: Английский

Citations

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

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

1
Natural compounds modulating mitophagy: Implications for cancer therapy DOI

Min Cao,

Yancheng Tang,

Yufei Luo

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 582, P. 216590 - 216590

Published: Dec. 12, 2023

Language: Английский

Citations

18
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

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 15 - 27

Published: April 27, 2024

Language: Английский

Citations

8
The interplay between autophagy and cGAS-STING signaling and its implications for cancer DOI Creative Commons
Maximilian Schmid, Patrick D. Fischer, Magdalena Engl

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 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

Language: Английский

Citations

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

Geneva L. Williams

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114294 - 114294

Published: May 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.

Language: Английский

Citations

5
Coordinating BNIP3/NIX-mediated mitophagy in space and time DOI Creative Commons
Natalie M. Niemi, Jonathan R. Friedman

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(5), P. 1969 - 1979

Published: Oct. 8, 2024

Mitochondria maintain organellar homeostasis through multiple quality control pathways, including the clearance of defective or unwanted mitochondria by selective autophagy. This removal mitochondria, mitophagy, is controlled in large part outer mitochondrial membrane mitophagy receptors BNIP3 and NIX. While it has long been appreciated that NIX mediate controlling recruitment autophagic machinery to surface, requirement for carefully spatiotemporal regulation receptor-mediated only recently come light. Several new factors regulate BNIP3/NIX-mediated pathway have emerged, various loss-of-function cell animal models revealed dire consequences their dysregulation. In this mini-review, we discuss insights into mechanisms roles highlight questions emerged from identification these regulators.

Language: Английский

Citations

5