Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein Turnover

Abstract

The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as adenosine triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside in or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space. Mitochondrial fission and fusion are performed by guanosine triphosphatases (GTPases) on the outer and inner mitochondrial membranes with the assistance of other mitochondrial proteins. Due to the essential nature of mitochondrial function for cellular homeostasis, regulation of mitochondrial dynamics is under strict control. Some of the mechanisms used to regulate the function of these proteins are post-translational proteolysis and/or turnover, and this review will discuss these mechanisms required for correct mitochondrial network organization.

Keywords: mitochondria; protein half-life; proteolysis; ubiquitin.

Figure 1

Essential components of human mitochondrial dynamics indicating post-translational ubiquitylation and proteolysis, protein localization and known modifying enzymes.

Figure 2

Essential components of mitochondrial dynamics in Saccharomyces cerevisiae, indicating ubiquitylation and proteolysis, protein localization and known modifying enzymes.