Protein Synthesis and Assembly in Mitochondrial Disorders

Abstract

Human mitochondrial DNA (mtDNA) codes for 13 polypeptides which constitute the central core of the oxidative phosphorylation (OXPHOS) complexes. The machinery for mitochondrial protein synthesis has a dual origin: a full set of tRNAs, as well as the 12S and 16S rRNAs are encoded in the mitochondrial genome, while most factors necessary for translation are encoded by nuclear genes. The mitochondrial translation apparatus is highly specialized in expressing membrane proteins, and couples the synthesis of proteins to the insertion into the mitochondrial inner membrane. In recent years it has become clear that defects of mitochondrial translation and protein assembly cause several mitochondrial disorders. Since direct studies on protein synthesis in human mitochondria are still a relatively difficult task, we owe our current knowledge of this field to the large amount of genetic and biochemical studies performed in the yeast Saccharomyces cerevisiae. These studies have allowed the identification of several genes involved in mitochondrial protein synthesis and assembly, and have provided insights into the conserved mechanisms of mitochondrial gene expression. In the present review we will discuss the most recent advances in the understanding of the mechanisms and factors that govern mammalian mitochondrial translation/protein insertion, as well as known pathologies associated with them.

Yeast AEP3p Is an Accessory Factor in Initiation of Mitochondrial Translation

“…This general translation initiation function is compatible with Aep3p inner membrane localization and specific involvement in ATP6/8 mRNA translation. Mitochondrial protein synthesis is known to occur on the matrix face of the inner membrane (43), where Aep3p is localized. Although Ellis et al (24) noted the dramatic loss of ATP6/8 expression, translation of nearly all of the mitochondrially encoded proteins was depressed in their aep3 deletion strain.…”

Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer

“…polypeptides that constitute the central core of the OXPHOS complex are translated [24]. Up-regulation of an elongation factor (GFM1) and 5 mitochondrial ribosomal …”

PGC‐1α activation as a therapeutic approach in mitochondrial disease

“…Many aspects of the regulation and synchronization of these processes are unknown. (29)(30)(31)(32). Unassembled subunits are degraded AAAproteases situated in the inner mitochondrial membranes (33).…”

“…An increasingly recognized class of mitochondrial disorders are defects in the mitochondrial translation machinery (2,25,32). Reported pathological mutations affect the mitochondrial ribosome (110)(111)(112), mitochondrial elongation factors (113)(114)(115) as well as mitochondrial tRNA synthases (116)(117)(118).…”