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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/11/1559 |
| _version_ | 1827702184045707264 |
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| author | Prasad Sulkshane Jonathan Ram Michael H Glickman |
| author_facet | Prasad Sulkshane Jonathan Ram Michael H Glickman |
| author_sort | Prasad Sulkshane |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T14:49:44Z |
| format | Article |
| id | doaj.art-5cc50cb500e4434d9e97b69e3204bfbc |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T14:49:44Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5cc50cb500e4434d9e97b69e3204bfbc2023-11-20T21:04:17ZengMDPI AGBiomolecules2218-273X2020-11-011011155910.3390/biom10111559Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic AdaptabilityPrasad Sulkshane0Jonathan Ram1Michael H Glickman2The Faculty of Biology, Technion Israel Institute of Technology, Haifa 32000, IsraelThe Faculty of Biology, Technion Israel Institute of Technology, Haifa 32000, IsraelThe Faculty of Biology, Technion Israel Institute of Technology, Haifa 32000, IsraelMitochondria 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.https://www.mdpi.com/2218-273X/10/11/1559mitochondriaubiquitinproteasomemitophagyautophagyproteolysis |
| spellingShingle | Prasad Sulkshane Jonathan Ram Michael H Glickman Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability Biomolecules mitochondria ubiquitin proteasome mitophagy autophagy proteolysis |
| 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 | mitochondria ubiquitin proteasome mitophagy autophagy proteolysis |
| url | https://www.mdpi.com/2218-273X/10/11/1559 |
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