Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability

Version 1 : Received: 25 October 2020 / Approved: 26 October 2020 / Online: 26 October 2020 (10:49:39 CET)

A peer-reviewed article of this Preprint also exists.

Sulkshane, P.; Ram, J.; Glickman, M.H. Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability. Biomolecules 2020, 10, 1559. Sulkshane, P.; Ram, J.; Glickman, M.H. Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability. Biomolecules 2020, 10, 1559.

Journal reference: Biomolecules 2020, 10, 1559
DOI: 10.3390/biom10111559

Abstract

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 ER and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination have 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 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 the basal function of mitochondria, metabolic implications, and possible therapeutic applications.

Subject Areas

Mitochondria; Ubiquitin; Proteasome; mitophagy; autophagy; proteolysis; protein import; Protein Quality Control; Metabolism

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