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Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability
Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697252/ https://www.ncbi.nlm.nih.gov/pubmed/33207558 http://dx.doi.org/10.3390/biom10111559 |
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author | Sulkshane, Prasad Ram, Jonathan Glickman, Michael H |
author_facet | Sulkshane, Prasad Ram, Jonathan Glickman, Michael H |
author_sort | Sulkshane, Prasad |
collection | PubMed |
description | Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The ubiquitin-proteasome system (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the Endoplasmic Reticulum (ER) and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination has remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial protein import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for basal function of mitochondria, metabolic implications, and possible therapeutic applications. |
format | Online Article Text |
id | pubmed-7697252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76972522020-11-29 Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability Sulkshane, Prasad Ram, Jonathan Glickman, Michael H Biomolecules Review Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The ubiquitin-proteasome system (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the Endoplasmic Reticulum (ER) and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination has remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial protein import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for basal function of mitochondria, metabolic implications, and possible therapeutic applications. MDPI 2020-11-16 /pmc/articles/PMC7697252/ /pubmed/33207558 http://dx.doi.org/10.3390/biom10111559 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Sulkshane, Prasad Ram, Jonathan Glickman, Michael H Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability |
title | Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability |
title_full | Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability |
title_fullStr | Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability |
title_full_unstemmed | Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability |
title_short | Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability |
title_sort | ubiquitination of intramitochondrial proteins: implications for metabolic adaptability |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697252/ https://www.ncbi.nlm.nih.gov/pubmed/33207558 http://dx.doi.org/10.3390/biom10111559 |
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