Mitochondrial degradation: Mitophagy and beyond

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

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A mitochondrial SCF‐FBXL4 ubiquitin E3 ligase complex degrades BNIP3 and NIX to restrain mitophagy and prevent mitochondrial disease

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(13)

Published: March 10, 2023

Language: Английский

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Mitophagy for cardioprotection

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Oct. 5, 2023

Abstract Mitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control including fusion and fission, degradation, biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are central organelle for maintaining cardiac function. Since adult cardiomyocytes humans rarely divide, number dysfunctional cannot easily be diluted through cell division. Thus, efficient degradation crucial to cellular Mitophagy, a specific form autophagy, major mechanism which damaged or unnecessary targeted eliminated. Mitophagy active at baseline response stress, plays an essential role cardiomyocytes. mediated multiple mechanisms heart, each these can partially compensate loss another mechanism. However, insufficient levels mitophagy eventually lead dysfunction development heart failure. In this review, we discuss molecular pathophysiology, with focus on recent findings field.

Language: Английский

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Mitophagy mediated by BNIP3 and NIX protects against ferroptosis by downregulating mitochondrial reactive oxygen species

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(5), P. 651 - 661

Published: March 22, 2024

Language: Английский

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Targeting mitophagy in neurodegenerative diseases

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

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The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Jan. 12, 2025

Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through continuous accumulation misfolded proteins and damaged organelles. This review delineates roles two complementary synergistic degradation systems, ubiquitin–proteasome system (UPS) autophagy-lysosome system, in organelles for intracellular recycling. We emphasize interconnected decision-making processes systems maintaining homeostasis, such as biophysical state substrates, receptor oligomerization potentials (e.g., p62), compartmentalization capacities membrane structures). Mitochondria, hubs respiration metabolism, are implicated tumorigenesis. In subsequent sections, we thoroughly examine mechanisms mitochondrial quality control (MQC) preserving human cells. Notably, explored relationships between dynamics (fusion fission) various MQC processes—including UPS, proteases, mitophagy—in context repair pathways. Finally, assessed potential targeting (including molecular chaperones, dynamics, mitophagy biogenesis) therapeutic strategies. Understanding underlying may offer novel insights future therapies. highlights UPS degrading proteins, emphasizing substrate states, oligomerization, homeostasis. Innovatively links coordination to examining interplay these pathways varying degrees damage.

Language: Английский

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A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass

Molecular Cell, Journal Year: 2023, Volume and Issue: 84(2), P. 327 - 344.e9

Published: Dec. 26, 2023

Language: Английский

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Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(2)

Published: Feb. 1, 2024

Depression is the most disabling neuropsychiatric disorder, causing difficulties in daily life activities and social interactions. The exact mechanisms of depression remain largely unclear. However, some studies have shown that mitochondrial dysfunction would play a crucial role occurrence development depression.

Language: Английский

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Hypoxic Adaptation of Mitochondria and its Impact on Tumor Cell Function

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

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Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD

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

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