The lysosome as a master regulator of iron metabolism

Rizzollo, Francesca; More, Sanket; Vangheluwe, Peter; Agostinis, Patrizia

doi:10.1016/j.tibs.2021.07.003

Cited by 117 publications

(91 citation statements)

References 137 publications

(196 reference statements)

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“…Although we observed that disrupting mTORC1, BORC, and ARL8B protected phagocytes from overfeeding similar to cathepsin, we can only speculate that this is due to an effect on phagolysosome resolution. As RBCs are iron-heavy cargo and lysosomes are master regulators of iron metabolism and trafficking (Rizzollo et al 2021), we predict that overfeeding RBCs could increase the availability of redox-active iron, which is known to damage cellular membranes via lipid oxidation and induce ferroptosis (Chen et al 2020). However, as iron is not membrane permeant, cells deficient in phagocytic steps from engulfing RBCs to phagolysosome resolution should be protected from the damage induced by cytosolic iron.…”

Section: Discussionmentioning

confidence: 99%

TORC1, BORC, ARL-8 cycling, and kinesin-1 drive vesiculation of cell corpse phagolysosomes

Fazeli

Levin‐Konigsberg

Bassik

et al. 2022

Preprint

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The dynamics of phagolysosomes leading to cargo clearance are important to provide cells with metabolites and avoid auto-immune responses, but little is known about how phagolysosomes finally resolve cell corpses and cell debris. We previously discovered that polar body phagolysosomes tubulate into small vesicles to facilitate corpse clearance within 1.5 hours in C. elegans. Here, we show that vesiculation depends on activating TORC1 through amino acid release by the solute transporter SLC-36.1. Downstream of TORC1, BLOC-1-related complex (BORC) recruits the Arf-like GTPase ARL-8 to the phagolysosome for tubulation. Disrupting the regulated GTP-GDP cycle of ARL-8 reduces tubulation, delays corpse clearance, and mislocalizes ARL-8 away from lysosomes. We also demonstrate that mammalian phagocytes use TORC1, BORC, and ARL8B to promote phagolysosomal degradation, confirming the conserved importance of this pathway. Thus, by observing single phagolysosomes over time, we identified the molecular pathway regulating phagolysosome vesiculation that promotes efficient resolution.

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Section: Discussionmentioning

confidence: 99%

TORC1, BORC, ARL-8 cycling, and kinesin-1 drive vesiculation of cell corpse phagolysosomes

Fazeli

Levin‐Konigsberg

Bassik

et al. 2022

Preprint

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“…Iron elements are crucial for fundamental cellular anabolic activities; however, ROS production-derived lipid-related ROS was highly associated with ferroptosis [93]. According to a previous study, gold-coated iron NPs-treated cancer cells underwent mitochondriamediated autophagy [71].…”

Section: Zvi-based Nps Induced Programmed Cell Deathmentioning

confidence: 99%

“…Lysosomes play a key role in the regulation of iron metabolism, they occupy a central position in iron homeostasis, and control cell-death signaling [93]. Lysosomes also play a pivotal role in the resistance of chemotherapy, by sequestering drugs in their acidic environment [94].…”

Section: Lysosomes and Acidic Tmementioning

confidence: 99%

From Microenvironment Remediation to Novel Anti-Cancer Strategy: The Emergence of Zero Valent Iron Nanoparticles

Yang

Wang

et al. 2022

Pharmaceutics

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Accumulated studies indicate that zero-valent iron (ZVI) nanoparticles demonstrate endogenous cancer-selective cytotoxicity, without any external electric field, lights, or energy, while sparing healthy non-cancerous cells in vitro and in vivo. The anti-cancer activity of ZVI-based nanoparticles was anti-proportional to the oxidative status of the materials, which indicates that the elemental iron is crucial for the observed cancer selectivity. In this thematic article, distinctive endogenous anti-cancer mechanisms of ZVI-related nanomaterials at the cellular and molecular levels are reviewed, including the related gene modulating profile in vitro and in vivo. From a material science perspective, the underlying mechanisms are also analyzed. In summary, ZVI-based nanomaterials demonstrated prominent potential in precision medicine to modulate both programmed cell death of cancer cells, as well as the tumor microenvironment. We believe that this will inspire advanced anti-cancer therapy in the future.

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“…This may be due to the fact that mitochondria are the major cellular cites of iron utilization. Iron is required for the synthesis of heme and Fe-S clusters that are essential cofactors of enzymes involved in the tricarboxylic acid (TCA) cycle and the respiratory chain ( Rizzollo et al, 2021 ). Accordingly, hearts from patients with anthracycline-related cardiomyopathy displayed higher iron levels in mitochondria, compared to those from patients with normal cardiac function or other types of heart failure ( Ichikawa et al, 2014 ).…”

Section: Mitochondrial Iron-overload and Ferroptosis During Anthracyc...mentioning

confidence: 99%

Understanding Anthracycline Cardiotoxicity From Mitochondrial Aspect

Huang

Chen

et al. 2022

Front. Pharmacol.

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Anthracyclines, such as doxorubicin, represent one group of chemotherapy drugs with the most cardiotoxicity. Despite that anthracyclines are capable of treating assorted solid tumors and hematological malignancies, the side effect of inducing cardiac dysfunction has hampered their clinical use. Currently, the mechanism underlying anthracycline cardiotoxicity remains obscure. Increasing evidence points to mitochondria, the energy factory of cardiomyocytes, as a major target of anthracyclines. In this review, we will summarize recent findings about mitochondrial mechanism during anthracycline cardiotoxicity. In particular, we will focus on the following aspects: 1) the traditional view about anthracycline-induced reactive oxygen species (ROS), which is produced by mitochondria, but in turn causes mitochondrial injury. 2) Mitochondrial iron-overload and ferroptosis during anthracycline cardiotoxicity. 3) Autophagy, mitophagy and mitochondrial dynamics during anthracycline cardiotoxicity. 4) Anthracycline-induced disruption of cardiac metabolism.

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The lysosome as a master regulator of iron metabolism

Cited by 117 publications

References 137 publications

TORC1, BORC, ARL-8 cycling, and kinesin-1 drive vesiculation of cell corpse phagolysosomes

TORC1, BORC, ARL-8 cycling, and kinesin-1 drive vesiculation of cell corpse phagolysosomes

From Microenvironment Remediation to Novel Anti-Cancer Strategy: The Emergence of Zero Valent Iron Nanoparticles

Understanding Anthracycline Cardiotoxicity From Mitochondrial Aspect

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