Mammalian pexophagy at a glance DOI Creative Commons

Justyna Bajdzienko,

Anja Bremm

Journal of Cell Science, Год журнала: 2024, Номер 137(9)

Опубликована: Май 1, 2024

ABSTRACT Peroxisomes are highly plastic organelles that involved in several metabolic processes, including fatty acid oxidation, ether lipid synthesis and redox homeostasis. Their abundance activity dynamically regulated response to nutrient availability cellular stress. Damaged or superfluous peroxisomes removed mainly by pexophagy, the selective autophagy of induced ubiquitylation peroxisomal membrane proteins ubiquitin-independent processes. Dysregulated pexophagy impairs peroxisome homeostasis has been linked development various human diseases. Despite many recent insights into mammalian our understanding this process is still limited compared yeast. In Cell Science at a Glance article accompanying poster, we summarize current knowledge on control highlight which aspects require further attention. We also discuss role describe ubiquitin machinery regulating signals for recruitment phagophores peroxisomes.

Язык: Английский

Pexophagy and Oxidative Stress: Focus on Peroxisomal Proteins and Reactive Oxygen Species (ROS) Signaling Pathways DOI Creative Commons
Xiaofan Wei,

Laxman Manandhar,

Hyunsoo Kim

и другие.

Antioxidants, Год журнала: 2025, Номер 14(2), С. 126 - 126

Опубликована: Янв. 23, 2025

Peroxisomes generate reactive oxygen species (ROS) and also play a role in protecting cells from the damaging effects of such radicals. Dysfunctional peroxisomes are recognized by receptors degraded selective type macroautophagy called pexophagy. Oxidative stress is one signals that activates pexophagy through multiple signaling pathways. Conversely, impaired results accumulation damaged peroxisomes, which turn leads to elevated ROS levels oxidative stress, resulting as cellular dysfunction progression diseases neurodegeneration, cancer, metabolic disorders. This review explores molecular mechanisms driving its regulation with particular focus on ROS. highlights peroxisomal proteins ROS-mediated pathways regulating In addition, emerging evidence suggests dysregulation closely linked neurological disorders, underscoring potential therapeutic target. Understanding intricate crosstalk between provides new insights into maintenance homeostasis offers promising directions for addressing disorders tightly associated stress.

Язык: Английский

Процитировано

1
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
TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1 DOI
François Le Guerroué, Eric Bunker, William M. Rosencrans

и другие.

Molecular Cell, Год журнала: 2023, Номер 83(6), С. 927 - 941.e8

Опубликована: Март 1, 2023

Язык: Английский

Процитировано

23
PINK1 regulated mitophagy is evident in skeletal muscles DOI Creative Commons
François Singh, Léa P. Wilhelm, Alan R. Prescott

и другие.

Autophagy Reports, Год журнала: 2024, Номер 3(1)

Опубликована: Март 11, 2024

PINK1, mutated in familial forms of Parkinson's disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically mice as loss PINK1 does not alter basal levels most tissues. To further characterize vivo, we used mito-QC which was combined with the mitochondrial-associated POLGD257A mutation. We focused on skeletal muscle gene expression data indicates that tissue has highest levels. found oxidative hindlimb significantly reduced mitophagy. Of interest, presence mutation, while having a minor effect tissues, restored caused by PINK1. Although our observations highlight multiple pathways operate within single tissue, identify choice for study PINK1-dependant under conditions.

Язык: Английский

Процитировано

9
When autophagy meets placenta development and pregnancy complications DOI Creative Commons
Pei Zhou, Junqi Wang, Jun Wang

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Фев. 2, 2024

Autophagy is a common biological phenomenon in eukaryotes that has evolved and reshaped to maintain cellular homeostasis. Under the pressure of starvation, hypoxia, immune damage, autophagy provides energy nutrients cells, which benefits cell survival. In mammals, an early embryonic nutrient supply system involved development, implantation, pregnancy maintenance. Recent studies have found imbalance placental tissue plays key role occurrence development complications, such as gestational hypertension, obesity, premature birth, miscarriage, intrauterine growth restriction. This mini-review summarizes molecular mechanism regulation, pathways, related factors comprehensively describes complications.

Язык: Английский

Процитировано

7
RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes DOI
Yifei Chen,

Fuji Yang,

Yujie Shi

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 219, С. 163 - 179

Опубликована: Апрель 13, 2024

Язык: Английский

Процитировано

7
Segregation of pathways leading to pexophagy DOI Creative Commons
Francesco G. Barone, Sylvie Urbé, Michael J. Clague

и другие.

Life Science Alliance, Год журнала: 2023, Номер 6(5), С. e202201825 - e202201825

Опубликована: Фев. 21, 2023

Peroxisomes are organelles with key roles in metabolism including long-chain fatty acid production. Their metabolic functions overlap and interconnect those of mitochondria, which they share an overlapping but distinct proteome. Both degraded by selective autophagy processes termed pexophagy mitophagy. Although mitophagy has received intense attention, the pathways linked to associated tools less well developed. We have identified neddylation inhibitor MLN4924 as a potent activator show that this is mediated HIF1α-dependent up-regulation BNIP3L/NIX, known adaptor for pathway from induced USP30 deubiquitylase CMPD-39, we identify NBR1 central player. Our work suggests level complexity regulation peroxisome turnover includes capacity coordinate mitophagy, via NIX, acts rheostat both processes.

Язык: Английский

Процитировано

16
The interplay between mitophagy and mitochondrial ROS in acute lung injury DOI

Yizhi Zhong,

Siwei Xia,

Gaojian Wang

и другие.

Mitochondrion, Год журнала: 2024, Номер 78, С. 101920 - 101920

Опубликована: Июнь 12, 2024

Язык: Английский

Процитировано

6
Opposing roles for AMPK in regulating distinct mitophagy pathways DOI Creative Commons

Marianna Longo,

Aniketh Bishnu,

Pierpaolo Risiglione

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(22), С. 4350 - 4367.e9

Опубликована: Ноя. 1, 2024

Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the receptors NIX BNIP3. Although AMP-activated protein kinase (AMPK), energy-sensing kinase, influence damaged-induced mitophagy, its role in is unclear. We found AMPK directly inhibits NIX-dependent by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 an additional identified site, Ser694. By contrast, activation increases Parkin enhances rate depolarization-induced independently ULK1. this happens both cultured cells tissues vivo, using mito-QC mouse model. Our work unveils a mechanism whereby downregulates mitochondria dysfunctional/damaged ones.

Язык: Английский

Процитировано

6
Coordinating BNIP3/NIX-mediated mitophagy in space and time DOI Creative Commons
Natalie M. Niemi, Jonathan R. Friedman

Biochemical Society Transactions, Год журнала: 2024, Номер 52(5), С. 1969 - 1979

Опубликована: Окт. 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.

Язык: Английский

Процитировано

5