Imperfect asymmetry: the mechanism governing asymmetric partitioning of damaged cellular components during mitosis
Imperfect asymmetry: the mechanism governing asymmetric partitioning of damaged cellular components during mitosis
Aging is universally associated with organism-wide dysfunction and a decline in cellular fitness. From early development onwards, the efficiency of self-repair, energy production, and homeostasis all decrease. Due to the multiplicity of systems that undergo agingrelated decline, the mechanistic basis of organismal aging has been difficult to pinpoint. At the cellular level, however, recent work has provided important insight. Cellular aging is associated with the accumulation of several types of damage, in particular damage to the proteome and organelles. Groundbreaking studies have shown that replicative aging is the result of a rejuvenation mechanism that prevents the inheritance of damaged components during division, thereby confining the effects of aging to specific cells, while removing damage from others. Asymmetric inheritance of misfolded and aggregated proteins, as well as reduced mitochondria, has been shown in yeast. Until recently, however, it was not clear whether a similar mechanism operates in mammalian cells, which were thought to mostly divide symmetrically. Our group has recently shown that vimentin establishes mitotic polarity in immortalized mammalian cells, and mediates asymmetric partitioning of multiple factors through direct interaction. These findings prompt a provocative hypothesis: that intermediate filaments serve as asymmetric partitioning modules or "sponges" that, when expressed prior to mitosis, can "clean" emerging cells of the damage they have accumulated.
Aging/metabolism, Animals, Cell Compartmentation, Cellular Senescence, Humans, Intermediate Filaments/metabolism, Mitosis, Protein Aggregates, Protein Aggregation, Pathological, Protein Folding, Proteolysis, Signal Transduction, Vimentin/metabolism
203-9
Pattabiraman, Sundararaghavan
a9f5aac6-6388-4b65-ba29-33aa47aad5a4
Kaganovich, Daniel
ebb13f4e-e925-4aef-88e7-ddc25ef52d8f
22 May 2015
Pattabiraman, Sundararaghavan
a9f5aac6-6388-4b65-ba29-33aa47aad5a4
Kaganovich, Daniel
ebb13f4e-e925-4aef-88e7-ddc25ef52d8f
Pattabiraman, Sundararaghavan and Kaganovich, Daniel
(2015)
Imperfect asymmetry: the mechanism governing asymmetric partitioning of damaged cellular components during mitosis.
Bioarchitecture, 4 (6), .
(doi:10.1080/19490992.2015.1014213).
Abstract
Aging is universally associated with organism-wide dysfunction and a decline in cellular fitness. From early development onwards, the efficiency of self-repair, energy production, and homeostasis all decrease. Due to the multiplicity of systems that undergo agingrelated decline, the mechanistic basis of organismal aging has been difficult to pinpoint. At the cellular level, however, recent work has provided important insight. Cellular aging is associated with the accumulation of several types of damage, in particular damage to the proteome and organelles. Groundbreaking studies have shown that replicative aging is the result of a rejuvenation mechanism that prevents the inheritance of damaged components during division, thereby confining the effects of aging to specific cells, while removing damage from others. Asymmetric inheritance of misfolded and aggregated proteins, as well as reduced mitochondria, has been shown in yeast. Until recently, however, it was not clear whether a similar mechanism operates in mammalian cells, which were thought to mostly divide symmetrically. Our group has recently shown that vimentin establishes mitotic polarity in immortalized mammalian cells, and mediates asymmetric partitioning of multiple factors through direct interaction. These findings prompt a provocative hypothesis: that intermediate filaments serve as asymmetric partitioning modules or "sponges" that, when expressed prior to mitosis, can "clean" emerging cells of the damage they have accumulated.
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Published date: 22 May 2015
Keywords:
Aging/metabolism, Animals, Cell Compartmentation, Cellular Senescence, Humans, Intermediate Filaments/metabolism, Mitosis, Protein Aggregates, Protein Aggregation, Pathological, Protein Folding, Proteolysis, Signal Transduction, Vimentin/metabolism
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Local EPrints ID: 475689
URI: http://eprints.soton.ac.uk/id/eprint/475689
ISSN: 1949-0992
PURE UUID: 01b66c18-5cc5-4f2b-8d78-aefb281fe19e
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Date deposited: 24 Mar 2023 17:55
Last modified: 17 Mar 2024 04:17
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Author:
Sundararaghavan Pattabiraman
Author:
Daniel Kaganovich
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