Cited by 287Autophagy in Disease and TherapyCalcium signaling and nucleotide metabolismGenetics, Aging, and Longevity in Model Organisms

Lysosomes and oxidative stress in aging and apoptosis

Kurz, Tino, Terman, Alexei, Gustafsson, Bertil, Brunk, Ulf T.·2008·Biochimica et Biophysica Acta (BBA) - General Subjects

Abstract

The lysosomal compartment consists of numerous acidic vesicles (pH approximately 4-5) that constantly fuse and divide. It receives a large number of hydrolases from the trans-Golgi network, while their substrates arrive from both the cell's outside (heterophagy) and inside (autophagy). Many macromolecules under degradation inside lysosomes contain iron that, when released in labile form, makes lysosomes sensitive to oxidative stress. The magnitude of generated lysosomal destabilization determines if reparative autophagy, apoptosis, or necrosis will follow. Apart from being an essential turnover process, autophagy is also a mechanism for cells to repair inflicted damage, and to survive temporary starvation. The inevitable diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow oxidative formation of lipofuscin in long-lived postmitotic cells, where it finally occupies a substantial part of the volume of the lysosomal compartment. This seems to result in a misdirection of lysosomal enzymes away from autophagosomes, resulting in depressed autophagy and the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. This scenario might put aging into the category of autophagy disorders.

Integrity signals

Registry

Crossref · 10.1016/j.bbagen.2008.01.009

Cites

128 of 128 references verified0 citation errors · 0 not checkable

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  • ROS play a prominent causal role in LMP, as H2O2-driven luminal production of hydroxyl radicals by Fenton reactions destabilizes the lysosomal membrane upon lipid peroxidation.

    “ROS play a prominent causal role in LMP, not only as the H2O2-driven luminal production of hydroxyl radicals by Fenton reactions destabilizes the lysosomal membrane upon lipid peroxidation [766, 767]”
  • Damaged mitochondria are insensitive to mitophagy, and consequently mitochondrial number and size are not properly regulated in senescent cells.

    “Moreover, damaged mitochondria are insensitive to mitophagy (i.e., selective autophagy of mitochondria), and consequently, mitochondrial number and size are not properly regulated in senescent cells [214].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [214]

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Authors
Kurz, T., Terman, A., Gustafsson, B., & Brunk, U. T.
Affiliations
  • Linköping University (SE)
  • Linköping University Hospital (SE)
Corresponding author
Brunk, Ulf T.
Venue
Biochimica et Biophysica Acta (BBA) - General Subjects
Publisher
Elsevier BV
Published
2008-11
Volume
1780
Issue
11
Pages
1291-1303
ISSN
0304-4165 (ISSN-L)
OpenAlex
W2056367295
Cited by
287
References
129
Citations by year
2026: 13 · 2025: 11 · 2024: 9 · 2023: 7 · 2022: 13 · 2021: 14 · 2020: 14 · 2019: 21 · 2018: 13 · 2017: 13 · 2016: 21 · 2015: 11 · 2014: 23 · 2013: 16 · 2012: 15
FWCI
2.56
Type
journal article
Language
en
Open access
closed
Locations
  • Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
lysosomes, oxidative stress, aging, apoptosis, autophagy, iron release, lipofuscin, lysosomal destabilization, hydrogen peroxide, mitochondrial dysfunction, lysosomal enzymes, necrosis, starvation survival
MeSH terms
Aging, Animals, Humans, Iron, Lysosomes, Mitosis, Apoptosis, Oxidative Stress

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