The Lysosome at the Intersection of Cellular Growth and Destruction

Developmental Cell, Год журнала: 2020, Номер 54(2), С. 226 - 238

Опубликована: Июнь 30, 2020

Язык: Английский

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Ironing out mechanisms of iron homeostasis and disorders of iron deficiency

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(11)

Опубликована: Июнь 1, 2021

Iron plays an important role in mammalian physiological processes. It is a critical component for the function of many proteins, including enzymes that require heme and iron-sulfur clusters. However, excess iron also detrimental because its ability to catalyze formation reactive oxygen species. As result, cellular systemic levels are tightly regulated prevent oxidative damage. deficiency can lead number pathological conditions, most prominent being anemia. should be corrected improve adult patients’ symptoms facilitate normal growth during fetal development childhood. inappropriate use intravenous chronic such as cancer heart failure, absence clear unwanted side effects. Thus, this form therapy reserved certain patients who cannot tolerate oral need rapid replenishment. Here, we will review homeostasis discuss complications deficiency.

Язык: Английский

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Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

PLoS Biology, Год журнала: 2021, Номер 19(12), С. e3001480 - e3001480

Опубликована: Дек. 16, 2021

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson disease (PD), while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase activity and induce neurotoxicity vitro vivo. The small GTPase Rab8a is a substrate involved receptor-mediated recycling endocytic trafficking of transferrin, but the effect on function poorly understood. Here, we show that gain-of-function sequestration endogenous to lysosomes overexpression cell models, pharmacological inhibition reverses this phenotype. Furthermore, drive association endocytosed transferrin Rab8a-positive lysosomes. has been nominated as an integral part cellular responses downstream proinflammatory signals activated microglia postmortem PD tissue. iPSC-derived from patients carrying most common mutation, G2019S, mistraffic proximal nucleus conditions. G2019S knock-in mice significant iron deposition following intrastriatal LPS injection compared wild-type mice, accompanied by striatal accumulation ferritin. Our data support role modulating uptake storage response stimuli microglia.

Язык: Английский

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Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance

Journal of Neuroimmune Pharmacology, Год журнала: 2021, Номер 16(2), С. 219 - 237

Опубликована: Март 22, 2021

Язык: Английский

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Canonical Wnt signaling works downstream of iron overload to prevent ferroptosis from damaging osteoblast differentiation

Free Radical Biology and Medicine, Год журнала: 2022, Номер 188, С. 337 - 350

Опубликована: Июнь 22, 2022

Язык: Английский

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