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Mitochondria inter-organelle relationships in cancer protein aggregation

Mitochondria are physically associated with other organelles, such as ER and lysosomes, forming a complex network that is crucial for cell homeostasis regulation. Inter-organelle relationships are finely regulated by both tether systems, which maintain physical proximity, and by signaling cues that...

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Autores principales: Genovese, Ilaria, Fornetti, Ersilia, Ruocco, Giancarlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806238/
https://www.ncbi.nlm.nih.gov/pubmed/36601538
http://dx.doi.org/10.3389/fcell.2022.1062993
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author Genovese, Ilaria
Fornetti, Ersilia
Ruocco, Giancarlo
author_facet Genovese, Ilaria
Fornetti, Ersilia
Ruocco, Giancarlo
author_sort Genovese, Ilaria
collection PubMed
description Mitochondria are physically associated with other organelles, such as ER and lysosomes, forming a complex network that is crucial for cell homeostasis regulation. Inter-organelle relationships are finely regulated by both tether systems, which maintain physical proximity, and by signaling cues that induce the exchange of molecular information to regulate metabolism, Ca(2+) homeostasis, redox state, nutrient availability, and proteostasis. The coordinated action of the organelles is engaged in the cellular integrated stress response. In any case, pathological conditions alter functional communication and efficient rescue pathway activation, leading to cell distress exacerbation and eventually cell death. Among these detrimental signals, misfolded protein accumulation and aggregation cause major damage to the cells, since defects in protein clearance systems worsen cell toxicity. A cause for protein aggregation is often a defective mitochondrial redox balance, and the ER freshly translated misfolded proteins and/or a deficient lysosome-mediated clearance system. All these features aggravate mitochondrial damage and enhance proteotoxic stress. This review aims to gather the current knowledge about the complex liaison between mitochondria, ER, and lysosomes in facing proteotoxic stress and protein aggregation, highlighting both causes and consequences. Particularly, specific focus will be pointed to cancer, a pathology in which inter-organelle relations in protein aggregation have been poorly investigated.
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spelling pubmed-98062382023-01-03 Mitochondria inter-organelle relationships in cancer protein aggregation Genovese, Ilaria Fornetti, Ersilia Ruocco, Giancarlo Front Cell Dev Biol Cell and Developmental Biology Mitochondria are physically associated with other organelles, such as ER and lysosomes, forming a complex network that is crucial for cell homeostasis regulation. Inter-organelle relationships are finely regulated by both tether systems, which maintain physical proximity, and by signaling cues that induce the exchange of molecular information to regulate metabolism, Ca(2+) homeostasis, redox state, nutrient availability, and proteostasis. The coordinated action of the organelles is engaged in the cellular integrated stress response. In any case, pathological conditions alter functional communication and efficient rescue pathway activation, leading to cell distress exacerbation and eventually cell death. Among these detrimental signals, misfolded protein accumulation and aggregation cause major damage to the cells, since defects in protein clearance systems worsen cell toxicity. A cause for protein aggregation is often a defective mitochondrial redox balance, and the ER freshly translated misfolded proteins and/or a deficient lysosome-mediated clearance system. All these features aggravate mitochondrial damage and enhance proteotoxic stress. This review aims to gather the current knowledge about the complex liaison between mitochondria, ER, and lysosomes in facing proteotoxic stress and protein aggregation, highlighting both causes and consequences. Particularly, specific focus will be pointed to cancer, a pathology in which inter-organelle relations in protein aggregation have been poorly investigated. Frontiers Media S.A. 2022-12-19 /pmc/articles/PMC9806238/ /pubmed/36601538 http://dx.doi.org/10.3389/fcell.2022.1062993 Text en Copyright © 2022 Genovese, Fornetti and Ruocco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Genovese, Ilaria
Fornetti, Ersilia
Ruocco, Giancarlo
Mitochondria inter-organelle relationships in cancer protein aggregation
title Mitochondria inter-organelle relationships in cancer protein aggregation
title_full Mitochondria inter-organelle relationships in cancer protein aggregation
title_fullStr Mitochondria inter-organelle relationships in cancer protein aggregation
title_full_unstemmed Mitochondria inter-organelle relationships in cancer protein aggregation
title_short Mitochondria inter-organelle relationships in cancer protein aggregation
title_sort mitochondria inter-organelle relationships in cancer protein aggregation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806238/
https://www.ncbi.nlm.nih.gov/pubmed/36601538
http://dx.doi.org/10.3389/fcell.2022.1062993
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