Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 94, P. 102493 - 102493
Published: March 21, 2025
Language: Английский
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 EMBO Journal, Journal Year: 2023, Volume and Issue: 42(13)
Published: May 10, 2023
Abstract To maintain both mitochondrial quality and quantity, cells selectively remove damaged or excessive mitochondria through mitophagy, which is a specialised form of autophagy. Mitophagy induced in response to diverse conditions, including hypoxia, cellular differentiation damage. However, the mechanisms that govern removal specific dysfunctional under steady‐state conditions fine‐tune content are not well understood. Here, we report SCF FBXL4 , an SKP1/CUL1/F‐box protein ubiquitin ligase complex, localises outer membrane unstressed mediates constitutive ubiquitylation degradation mitophagy receptors NIX BNIP3 suppress basal levels mitophagy. We demonstrate pathogenic variants cause encephalopathic mtDNA depletion syndrome (MTDPS13) do efficiently interact with core machinery mediate BNIP3. Thus, reveal molecular mechanism whereby actively suppresses by preventing accumulation. propose dysregulation turnover causes FBXL4‐associated syndrome.
Language: Английский
Citations
48
Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(5), P. 651 - 661
Published: March 22, 2024
Language: Английский
Citations
22
Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 14, 2025
Language: Английский
Citations
12
Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102667 - 102667
Published: Jan. 1, 2025
Language: Английский
Citations
3
Molecular Cell, Journal Year: 2023, Volume and Issue: 84(2), P. 327 - 344.e9
Published: Dec. 26, 2023
Language: Английский
Citations
28
Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 100, P. 28 - 38
Published: March 30, 2024
Mitochondria are the major sink for oxygen in cell, consuming it during ATP production. Therefore, when environmental levels drop tumor, significant adaptation is required. Mitochondrial activity also a producer of biosynthetic precursors and regulator cellular oxidative reductive balance. Because complex biochemistry, mitochondrial to hypoxia occurs through multiple mechanisms has impact on other processes such as macromolecule synthesis gene regulation. In tumor hypoxia, mitochondria shift their location cell accelerate fission quality control pathways. Hypoxic undergo changes fundamental metabolic pathways carbon metabolism electron transport. These further nuclear epigenome because metabolites used enzymatic substrates modifying chromatin. This coordinated response delivers physiological flexibility increased robustness stress low oxygen.
Language: Английский
Citations
12
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
11
EMBO Reports, Journal Year: 2024, Volume and Issue: 25(8), P. 3324 - 3347
Published: July 11, 2024
Language: Английский
Citations
9
Autophagy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19
Published: Sept. 12, 2024
Uveal melanoma (UM) is an aggressive intraocular malignancy derived from melanocytes in the uvea tract of eye. Up to 50% patients with UM develop distant metastases which usually fatal within one year; preventing therefore essential. Metabolic reprogramming plays a critical role progression and metastasis. However, metabolic phenotype cells hypoxic tumor not well understood. Here, we report that hypoxia-induced BNIP3 reprograms cell metabolism, promoting their survival In response hypoxia, BNIP3-mediated mitophagy alleviates mitochondrial dysfunction enhances oxidative phosphorylation (OXPHOS) while simultaneously reducing reactive oxygen species (mtROS) production. This, turn, impairs HIF1A/HIF-1α protein stability inhibits glycolysis. Inhibition significantly suppresses BNIP3-induced metastasis
Language: Английский
Citations
9