The lysosome as a master regulator of iron metabolism

Trends in Biochemical Sciences, Journal Year: 2021, Volume and Issue: 46(12), P. 960 - 975

Published: Aug. 9, 2021

Language: Английский

---

Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

---

Cerebral Iron Deposition in Neurodegeneration

Biomolecules, Journal Year: 2022, Volume and Issue: 12(5), P. 714 - 714

Published: May 17, 2022

Disruption of cerebral iron regulation appears to have a role in aging and the pathogenesis various neurodegenerative disorders. Possible unfavorable impacts accumulation include reactive oxygen species generation, induction ferroptosis, acceleration inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow examination macroscopic patterns brain deposits vivo, while modern analytical methods ex vivo enable determination metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes whole brain, cellular, subcellular diseases genetic sporadic origin. We provide an update on mechanisms, biomarkers, effects these disorders, focusing recent publications. In Parkinson’s disease, Friedreich’s several disorders neurodegeneration with group, there is focal siderosis, typically regions most pronounced neuropathological second group including multiple sclerosis, Alzheimer’s amyotrophic lateral sclerosis shows globus pallidus, caudate, putamen, cortical regions. Yet, other such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest diffuse deep gray matter pattern comparable even more extensive than that observed during normal aging. On microscopic level, are mostly dystrophic microglia variably accompanied by iron-laden macrophages astrocytes, implicating changes blood–brain barrier disturbance accumulation. Options potential benefits reducing strategies discussed. Future research investigating whether predispositions play Fe necessary. If confirmed, prevention further uptake individuals at risk may be key for preventing

Language: Английский

---

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications

Physiological Reviews, Journal Year: 2022, Volume and Issue: 102(4), P. 1625 - 1667

Published: April 4, 2022

For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from glomerular filtrate. Innovative techniques approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chronic kidney disease (CKD), acute injury lead significant albuminuria, reaching nephrotic range. Albumin is also stimulate cascades. Thus, mechanisms of reabsorption, catabolism, transcytosis are being reexamined with use that allow for novel molecular cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, Dab2 form multireceptor complex mediates binding uptake directs proteins lysosomal degradation after endocytosis. mediated by pH-dependent affinity neonatal Fc receptor (FcRn) in endosomal compartments. This reclamation pathway rescues urinary losses extending its serum half-life. altered oxidation, glycation, carbamylation because other bound ligands do not bind FcRn traffics lysosome. sorting mechanism reclaims physiological eliminates potentially toxic albumin. The clinical importance metabolism increased as now used therapeutic agents extend their half-life minimize filtration injury. purpose this review update integrate evolving information regarding reabsorption processing cells including discussion disorders considerations.

Language: Английский

---

Organelle transporters and inter-organelle communication as drivers of metabolic regulation and cellular homeostasis

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 60, P. 101481 - 101481

Published: March 25, 2022

Spatial compartmentalization of metabolic pathways within membrane-separated organelles is key to the ability eukaryotic cells precisely regulate their biochemical functions. Membrane-bound such as mitochondria, endoplasmic reticulum (ER) and lysosomes enable concentration precursors optimized chemical environments, greatly accelerating efficiency both anabolic catabolic reactions, enabling division labor optimal utilization resources. However, also poses a challenge because it creates spatial discontinuities that must be bridged for reaction cascades connected completed. To do so, employ different methods coordinate fluxes occurring in organelles, membrane-localized transporters facilitate regulated metabolite exchange between mitochondria lysosomes, non-vesicular transport via physical contact sites connecting ER with well localized regulatory signaling processes coordinately activity all these organelles.

Language: Английский

---

An overview of ferroptosis in non-alcoholic fatty liver disease

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 153, P. 113374 - 113374

Published: July 11, 2022

Non-alcoholic fatty liver disease (NAFLD) is a public health problem associated with high mortality and morbidity rates worldwide. Presently, its complex pathophysiology still unclear, there no specific drug to reverse NAFLD. Ferroptosis an iron-dependent non-apoptotic form of cell death characterized by the iron-induced accumulation lipid reactive oxygen species (ROS), which damage nucleic acids, proteins, lipids; generate intracellular oxidative stress; ultimately cause death. Emerging evidence indicates that ferroptosis involved in progression NAFLD, although mechanism action NAFLD poorly understood. Herein, we summarize certain diseases, especially pathogenesis discuss potential therapeutic approaches currently used treat This review also highlights further directions for treatment prevention related diseases.

Language: Английский

---

ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling

The Journal of Cell Biology, Journal Year: 2022, Volume and Issue: 221(7)

Published: June 3, 2022

Mutations in VPS13C cause early-onset, autosomal recessive Parkinson’s disease (PD). We have established that encodes a lipid transfer protein localized to contact sites between the ER and late endosomes/lysosomes. In current study, we demonstrate depleting HeLa cells causes an accumulation of lysosomes with altered profile, including di-22:6-BMP, biomarker PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation. addition, DNA-sensing cGAS-STING pathway, which was recently implicated PD pathogenesis, is activated these cells. This activation results from combination elevated mitochondrial DNA cytosol defect degradation STING, lysosome-dependent process. These suggest link ER-lysosome innate immune model human cell line place pathways relevant pathogenesis.

Language: Английский

---

Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(11), P. 926 - 946

Published: Aug. 6, 2024

Language: Английский

---

Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 5, 2023

Microglia are the resident innate immune cells in brain with a major role orchestrating responses. They also provide frontline of host defense central nervous system (CNS) through their active phagocytic capability. Being professional phagocyte, microglia participate and autophagic clearance cellular waste debris as well toxic protein aggregates, which relies on optimal lysosomal acidification function. Defective microglial leads to impaired functions result perpetuation neuroinflammation progression neurodegeneration. Reacidification lysosomes has been shown reverse neurodegenerative pathology Alzheimer's disease. In this review, we summarize key factors mechanisms contributing impairment associated dysfunction microglia, how these defects contribute We further discuss techniques monitor pH therapeutic agents that can reacidify under disease conditions. Finally, propose future directions investigate lysosome-mitochondria crosstalk neuron-glia interaction for more comprehensive understanding its broader CNS physiological pathological implications.

Language: Английский

---

Similarities and interplay between senescent cells and macrophages

The Journal of Cell Biology, Journal Year: 2020, Volume and Issue: 220(2)

Published: Dec. 2, 2020

Senescence is a cellular program that prevents the replication of old, damaged, or cancerous cells. Senescent cells become growth arrested and undergo changes in their morphology, chromatin organization, metabolism, produce bioactive secretome. This secretome, senescence-associated secretory phenotype (SASP), mediates many pathophysiological effects associated with senescent cells, for example, recruiting activating immune such as macrophages. The relation between macrophages intriguing: recruit macrophages, can induce them to senescence, influence polarization. share multiple phenotypic characteristics; both have high status, increased lysosome numbers, ability activate inflammasome. accumulate during aging disease, killing results widespread benefits. Here we discuss similarities interpret latest developments macrophage biology understand molecular mechanisms senescence. We describe evidence senescence speculate on ontogeny senescent-like state Finally, examine macrophage–senescent cell interplay its impact effector functions inflammatory conditions tumor microenvironment.

Language: Английский

---