Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia DOI Creative Commons
Shiping Zhang, Shuanglong Yi, Linfang Wang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(29)

Published: July 10, 2023

Autophagy is a major means for the elimination of protein inclusions in neurons neurodegenerative diseases such as Parkinson’s disease (PD). Yet, mechanism autophagy other brain cell type, glia, less well characterized and remains largely unknown. Here, we present evidence that PD risk factor, Cyclin-G-associated kinase (GAK)/ Drosophila homolog Auxilin (dAux), component glial autophagy. The lack GAK/dAux increases autophagosome number size adult fly glia mouse microglia, generally up-regulates levels components initiation PI3K class III complexes. interacts with master regulator UNC-51like activating 1/Atg1 via its uncoating domain regulates trafficking Atg1 Atg9 to autophagosomes, hence controlling onset On hand, impairs autophagic flux blocks substrate degradation, suggesting might play additional roles. Importantly, dAux contributes PD-like symptoms including dopaminergic neurodegeneration locomotor function flies. Our findings identify an factor glia; considering pivotal role under pathological conditions, targeting potentially therapeutic strategy PD.

Language: Английский

Mitophagy in human health, ageing and disease DOI
Anna Picca, Julie Faitg, Johan Auwerx

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(12), P. 2047 - 2061

Published: Nov. 30, 2023

Language: Английский

Citations

185
PINK1/Parkin-mediated mitophagy in neurodegenerative diseases DOI
Jie Li, Dongming Yang, Zhiping Li

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 84, P. 101817 - 101817

Published: Dec. 9, 2022

Language: Английский

Citations

153
Mitochondrial degradation: Mitophagy and beyond DOI Creative Commons
Louise Uoselis, Thanh Ngoc Nguyen, Michael Lazarou

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(19), P. 3404 - 3420

Published: Oct. 1, 2023

Mitochondria are central hubs of cellular metabolism that also play key roles in signaling and disease. It is therefore fundamentally important mitochondrial quality activity tightly regulated. Mitochondrial degradation pathways contribute to control networks can regulate the metabolic profile mitochondria ensure homeostasis. Here, we cover many varied ways which cells degrade or remove their unwanted mitochondria, ranging from mitophagy extrusion. The molecular signals driving these discussed, including physiological contexts under different engaged.

Language: Английский

Citations

117
The investigation on stress mechanisms of Sepia esculenta larvae in the context of global warming and ocean acidification DOI Creative Commons
Yongjie Wang, Xiumei Liu,

Weijun Wang

et al.

Aquaculture Reports, Journal Year: 2024, Volume and Issue: 36, P. 102120 - 102120

Published: May 8, 2024

Sepia esculenta is a tasty and nutritious cephalopod. But the trend toward global warming accelerating with massive emissions of greenhouse gases. An increase in seawater temperature decrease pH are great challenge for artificial breeding culture S. esculenta. In this study, we investigated contingency mechanism larvae under both high low conditions by transcriptome analysis. A total 1235 DEGs were identified. functional enrichment analysis results suggest that led to malignant proliferation exceptional cells larvae. comprehensive KEGG signaling pathway protein-protein interaction network (PPI) identified sixteen key genes conditions. The three highest quantities interactions or involved more pathways as hub affecting normal physiological processes effects ocean acidification on metabolism immunity preliminarily provide necessary help captive face climate change.

Language: Английский

Citations

20
Role of Mitophagy in Regulating Intestinal Oxidative Damage DOI Creative Commons
Xiaobin Wen, Lixin Tang, Ruqing Zhong

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 480 - 480

Published: Feb. 14, 2023

The mitochondrion is also a major site for maintaining redox homeostasis between reactive oxygen species (ROS) generation and scavenging. quantity, quality, functional integrity of mitochondria are crucial regulating intracellular the normal physiological function cells. role oxidative stress in human disease well established, particularly inflammatory bowel gastrointestinal mucosal diseases. Oxidative could result from an imbalance ROS antioxidative system. Mitochondria both main sites production target ROS. It vicious cycle which initial ROS-induced mitochondrial damage enhanced that, turn, leads to further eventually massive intestinal cell death. can be significantly mitigated by mitophagy, clears damaged mitochondria. In this review, we aimed review molecular mechanisms involved regulation mitophagy their relationship some We believe reviews provide new ideas scientific basis researching antioxidants preventing diseases related damage.

Language: Английский

Citations

36
SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics DOI Creative Commons
Laura Trachsel-Moncho,

Chiara Veroni,

Benan John Mathai

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(5)

Published: March 7, 2025

We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy OXPHOS machinery components. In control conditions, localizes to early endocytic compartments in PtdIns3P-dependent manner and modulates trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking late structures containing selected mitochondrial proteins, including COX-IV SAMM50, autophagy proteins SQSTM1/p62 LC3B. The turnover was enhanced SNX10-depleted cells, corresponding reduced respiration citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show levels Cox-IV, well elevated ROS ROS-mediated cell death brain, demonstrating vivo relevance SNX10-mediated modulation bioenergetics.

Language: Английский

Citations

1
Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1 DOI Creative Commons
Odetta Antico, Alban Ordureau, Michael Stevens

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(46)

Published: Nov. 12, 2021

Identification of neuronal targets PD-linked enzyme Parkin by quantitative ubiquitin-based proteomics.

Language: Английский

Citations

51
DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion DOI Creative Commons
Maeve Long, Álvaro Sánchez-Martínez,

Marianna Longo

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(10)

Published: April 12, 2022

Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether is a cause or consequence of such state changes. The signalling pathways that integrate to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated deferiprone, therapeutic iron chelator stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling lipid metabolism within minutes treatment. DGAT1-dependent droplet biosynthesis occurred several hours before mitochondrial clearance, droplets bordering upon chelation. demonstrate DGAT1 inhibition restricts in vitro, impaired homeostasis viability. Importantly, genetic vivo significantly neuronal locomotor function Drosophila. Our data define as potent signal rapidly reshapes establishes an unexpected synergy between safeguards integrity.

Language: Английский

Citations

33
Diversity of mitophagy pathways at a glance DOI Creative Commons
Ian G. Ganley, Anne Simonsen

Journal of Cell Science, Journal Year: 2022, Volume and Issue: 135(23)

Published: Dec. 1, 2022

Mitochondria are crucial organelles that play a central role in various cell signaling and metabolic pathways. A healthy mitochondrial population is maintained through series of quality control pathways requires fine-tuned balance between biogenesis degradation. Defective targeting dysfunctional mitochondria to lysosomes mitophagy has been linked several diseases, but the underlying mechanisms relative importance distinct vivo largely unknown. In this Cell Science at Glance accompanying poster, we describe our current understanding how parts of, or whole, recognized by autophagic machinery targeted for We also discuss might be regulated under different physiological conditions maintain cellular health.

Language: Английский

Citations

31
The cholesterol transport protein GRAMD1C regulates autophagy initiation and mitochondrial bioenergetics DOI Creative Commons
Matthew Yoke Wui Ng,

Chara Charsou,

Ana Lapao

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 21, 2022

Abstract During autophagy, cytosolic cargo is sequestered into double-membrane vesicles called autophagosomes. The contributions of specific lipids, such as cholesterol, to the membranes that form autophagosome, remain be fully characterized. Here, we demonstrate short term cholesterol depletion leads a rapid induction autophagy and corresponding increase in initiation events. We further show ER-localized transport protein GRAMD1C functions negative regulator starvation-induced both its VASt domain membrane binding GRAM are required for GRAMD1C-mediated suppression initiation. Similar yeast orthologue, associates with mitochondria through domain. Cells lacking or increased mitochondrial levels oxidative phosphorylation, suggesting may facilitate transfer at ER-mitochondria contact sites. Finally, expression GRAMD family proteins linked clear cell renal carcinoma survival, highlighting pathophysiological relevance proteins.

Language: Английский

Citations

30