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Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability

The Faculty of Biology, Technion Israel Institute of Technology, Haifa 32000, Israel
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Biomolecules 2020, 10(11), 1559; https://doi.org/10.3390/biom10111559
Received: 25 October 2020 / Revised: 11 November 2020 / Accepted: 12 November 2020 / Published: 16 November 2020
(This article belongs to the Special Issue Ubiquitin-Like Modifiers and Their Diverse Impact on Cell Signaling)
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. View Full-Text
Keywords: mitochondria; ubiquitin; proteasome; mitophagy; autophagy; proteolysis; protein import; protein quality control; metabolism mitochondria; ubiquitin; proteasome; mitophagy; autophagy; proteolysis; protein import; protein quality control; metabolism
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MDPI and ACS Style

Sulkshane, P.; Ram, J.; Glickman, M.H. Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability. Biomolecules 2020, 10, 1559. https://doi.org/10.3390/biom10111559

AMA Style

Sulkshane P, Ram J, Glickman MH. Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability. Biomolecules. 2020; 10(11):1559. https://doi.org/10.3390/biom10111559

Chicago/Turabian Style

Sulkshane, Prasad, Jonathan Ram, and Michael H. Glickman. 2020. "Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability" Biomolecules 10, no. 11: 1559. https://doi.org/10.3390/biom10111559

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