The cell biology of ferroptosis

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

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Mitochondria at the crossroads of health and disease

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2601 - 2627

Published: May 1, 2024

Mitochondria reside at the crossroads of catabolic and anabolic metabolism—the essence life. How their structure function are dynamically tuned in response to tissue-specific needs for energy, growth repair, renewal is being increasingly understood. respond intrinsic extrinsic stresses can alter cell organismal by inducing metabolic signaling within cells distal tissues. Here, we review how centrality mitochondrial functions manifests health a broad spectrum diseases aging.

Language: Английский

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Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7

Nature Cell Biology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 19, 2023

Abstract Coenzyme Q (or ubiquinone) is a redox-active lipid that serves as universal electron carrier in the mitochondrial respiratory chain and antioxidant plasma membrane limiting peroxidation ferroptosis. Mechanisms allowing cellular coenzyme distribution after synthesis within mitochondria are not understood. Here we identify cytosolic transfer protein STARD7 critical factor of intracellular transport suppressor Dual localization to intermembrane space cytosol upon cleavage by rhomboid protease PARL ensures its membrane. While preserves synthesis, oxidative phosphorylation function cristae morphogenesis, required for protects against A variant competes with phosphatidylcholine binding purified vitro. Overexpression increases ferroptotic resistance cells, but limits abundance cell growth. Our findings thus demonstrate need coordinate PARL-mediated processing promising targets interfere

Language: Английский

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A guideline on the molecular ecosystem regulating ferroptosis

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1447 - 1457

Published: Feb. 29, 2024

Language: Английский

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Mitochondrial integrated stress response controls lung epithelial cell fate

Nature, Journal Year: 2023, Volume and Issue: 620(7975), P. 890 - 897

Published: Aug. 9, 2023

Abstract Alveolar epithelial type 1 (AT1) cells are necessary to transfer oxygen and carbon dioxide between the blood air. 2 (AT2) serve as a partially committed stem cell population, producing AT1 during postnatal alveolar development repair after influenza A SARS-CoV-2 pneumonia 1–6 . Little is known about metabolic regulation of fate lung cells. Here we report that deleting mitochondrial electron transport chain complex I subunit Ndufs2 in mouse gestation led death development. Affected mice displayed hypertrophic with AT2 features, transitional Mammalian I, comprising 45 subunits, regenerates NAD + pumps protons. Conditional expression yeast NADH dehydrogenase (NDI1) protein without proton pumping 7,8 was sufficient correct abnormal avert lethality. Single-cell RNA sequencing revealed enrichment integrated stress response (ISR) genes Administering an ISR inhibitor 9,10 or precursor reduced gene signatures rescued lethality absence function. Notably, epithelial-specific loss II Sdhd , which maintains regeneration, did not trigger high activation These findings highlight unanticipated requirement for I-dependent regeneration directing by preventing pathological induction.

Language: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1620 - 1631

Published: Aug. 23, 2023

Abstract Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular neurodegeneration, liver disease, cancer. Although polyunsaturated fatty acids (PUFAs) membrane phospholipids are preferentially oxidized, saturated/monounsaturated (SFAs/MUFAs) also influence peroxidation ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs PUFAs they control acid pools via uptake β-oxidation, impacting Furthermore, discuss stored different lipids, diacyl or ether with head groups; triglycerides; cholesterols. Moreover, these released from molecules. summary, provide an integrated view the diverse dynamic metabolic processes context ferroptosis revisiting lipidomic studies. Thus, review development therapeutic strategies for ferroptosis-related diseases.

Language: Английский

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Ferroptosis in mitochondrial cardiomyopathy

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(2), P. 150 - 160

Published: July 5, 2023

Language: Английский

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A mitochondrial iron-responsive pathway regulated by DELE1

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(12), P. 2059 - 2076.e6

Published: June 1, 2023

Language: Английский

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Mitochondrial Structure and Function in Human Heart Failure

Circulation Research, Journal Year: 2024, Volume and Issue: 135(2), P. 372 - 396

Published: July 4, 2024

Despite clinical and scientific advancements, heart failure is the major cause of morbidity mortality worldwide. Both mitochondrial dysfunction inflammation contribute to development progression failure. Although crucial reparative healing following acute cardiomyocyte injury, chronic damages heart, impairs function, decreases cardiac output. Mitochondria, which comprise one third volume, may prove a potential therapeutic target for Known primarily energy production, mitochondria are also involved in other processes including calcium homeostasis regulation cellular apoptosis. Mitochondrial function closely related morphology, alters through dynamics, thus ensuring that needs cell met. However, failure, changes substrate use lead impaired myocyte function. This review discusses cristae role contact site organizing system complex ultrastructure changes. Additionally, this covers mitochondria-endoplasmic reticulum sites, communication via nanotunnels, altered metabolite production during We highlight these often-neglected factors promising targets

Language: Английский

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