Autophagy, organelles and ageing

Terman, Alexei; Gustafsson, Bertil; Brunk, Ulf T.

doi:10.1002/path.2094

Cited by 262 publications

(216 citation statements)

References 109 publications

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“…1). Here a variety of organelles and proteins are degraded into their building blocks, which in turn are reutilized by the anabolic machinery of the cell following their transport to the cytosol (reviewed in Klionsky, 2007, Terman et al, 2007. From a physiological point of view, the lysosomal compartment can be looked upon as a box, built of vacuoles that constantly fuse and divide, that receives enzymes from the TGN and substrates from either the outside or the inside of the cell.…”

Section: The Role Of Lysosomes In Intracellular Iron Metabolismmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

172

134

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Iron is the most abundant transition metal in the earths crust. It cycles easily between ferric (oxidized; Fe(III)) and ferrous (reduced; Fe(II)) and readily forms complexes with oxygen, making this metal a central player in respiration and related redox processes. However, loose iron, not within heme or iron-sulfur cluster proteins, can be destructively redox-active, causing damage to almost all cellular components, killing both cells and organisms. This may explain why iron is so carefully handled by aerobic organisms. Iron uptake from the environment is carefully limited and carried out by specialized iron transport mechanisms. One reason that iron uptake is tightly controlled is that most organisms and cells cannot efficiently excrete excess iron. When even small amounts of intracellular free iron occur, most of it is safely stored in a non-redox-active form in ferritins. Within nucleated cells, iron is constantly being recycled from aged iron-rich organelles such as mitochondria and used for construction of new organelles. Much of this recycling occurs within the lysosome, an acidic digestive organelle. Because of this, most lysosomes contain relatively large amounts of redox-active iron and are therefore unusually susceptible to oxidant-mediated destabilization or rupture. In many cell types, iron transit through the lysosomal compartment can be remarkably brisk. However, conditions adversely affecting lysosomal iron handling (or oxidant stress) can contribute to a variety of acute and chronic diseases. These considerations make normal and abnormal lysosomal handling of iron central to the understanding and, perhaps, therapy of a wide range of diseases

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Section: The Role Of Lysosomes In Intracellular Iron Metabolismmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

172

134

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“…Behl and coworkers demonstrated that BAG-3 levels are upregulated in aged neuronal cells, resulting in an increased targeting of oxidized and ubiquitylated proteins to the lysosome for disposal (Gamerdinger et al, 2009). The induction of BAG-3 mediated CASA apparently represents an important adaptation of the protein quality control system of neuronal cells to maintain proteostasis in the presence of an enhanced prooxidant and aggregation-prone milieu characteristic of aging (Terman et al, 2007).…”

Section: Casa: Chaperone-assisted Selective Autophagymentioning

confidence: 99%

Chaperone-assisted degradation: multiple paths to destruction

Kettern

Dreiseidler

Tawo³

et al. 2010

Biological Chemistry

152

155

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Molecular chaperones are well known as facilitators of protein folding and assembly. However, in recent years multiple chaperone-assisted degradation pathways have also emerged, including CAP ( haperone-ssisted roteasomal degradac a p tion), CASA ( haperone-ssisted elective utophagy), and c a s a CMA ( haperone-ediated utophagy). Within these pathc m a ways chaperones facilitate the sorting of non-native proteins to the proteasome and the lysosomal compartment for disposal. Impairment of these pathways contributes to the development of cancer, myopathies, and neurodegenerative diseases. Chaperone-assisted degradation thus represents an essential aspect of cellular proteostasis, and its pharmacological modulation holds the promise to ameliorate some of the most devastating diseases of our time. Here, we discuss recent insights into molecular mechanisms underlying chaperone-assisted degradation in mammalian cells and highlight its biomedical relevance.

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“…13 This formation of hydroxyl radicals results in enhanced lipid peroxidation of membranes, and consequent LMP. 14 Scavenging iron in therapy, using metal-protein-attenuating compounds, has been proven to be beneficial in neurodegenerative diseases, thereby making inhibition of LMP and consequent necrosis an interesting therapeutic strategy. 15 The different subcellular events in necrotic signaling are elusive.…”

mentioning

confidence: 99%

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

et al. 2009

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Necroptosis, necrosis and secondary necrosis following apoptosis represent different modes of cell death that eventually result in similar cellular morphology including rounding of the cell, cytoplasmic swelling, rupture of the plasma membrane and spilling of the intracellular content. Subcellular events during tumor necrosis factor (TNF)-induced necroptosis, H2O2-induced necrosis and anti-Fas-induced secondary necrosis were studied using high-resolution time-lapse microscopy. The cellular disintegration phase of the three types of necrosis is characterized by an identical sequence of subcellular events, including oxidative burst, mitochondrial membrane hyperpolarization, lysosomal membrane permeabilization and plasma membrane permeabilization, although with different kinetics. H2O2-induced necrosis starts immediately by lysosomal permeabilization. In contrast, during TNF-mediated necroptosis and anti-Fas-induced secondary necrosis, this is a late event preceded by a defined signaling phase. TNF-induced necroptosis depends on receptor-interacting protein-1 kinase, mitochondrial complex I and cytosolic phospholipase A(2) activities, whereas H2O2-induced necrosis requires iron-dependent Fenton reactions

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Autophagy, organelles and ageing

Cited by 262 publications

References 109 publications

The role of lysosomes in iron metabolism and recycling

The role of lysosomes in iron metabolism and recycling

Chaperone-assisted degradation: multiple paths to destruction

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

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