Mitochondrial translation defects and human disease.

Bryn D Webb,George A Diaz,Pankaj Prasun

doi:10.20517/jtgg.2020.11

Abstract

In eukaryotic cells, mitochondria perform the essential function of producing cellular energy in the form of ATP via the oxidative phosphorylation system. This system is composed of 5 multimeric protein complexes of which 13 protein subunits are encoded by the mitochondrial genome: Complex I (7 subunits), Complex III (1 subunit),Complex IV (3 subunits), and Complex (2 subunits). Effective mitochondrial translation is necessary to produce the protein subunits encoded by the mitochondrial genome (mtDNA). Defects in mitochondrial translation are known to cause a wide variety of clinical disease in humans with high-energy consuming organs generally most prominently affected. Here, we review several classes of disease resulting from defective mitochondrial translation including disorders with mitochondrial tRNA mutations, mitochondrial aminoacyl-tRNA synthetase disorders, mitochondrial rRNA mutations, and mitochondrial ribosomal protein disorders.

Highlights

Mitochondria are double-membrane bound organelles found in most eukaryotic organisms with the important function of generating cellular energy via oxidative phosphorylation, but which function in cellular signaling, cellular differentiation, cell death, and cell cycle regulation
Mitochondria are estimated to be comprised of approximately 1100 proteins and are unique organelles in that they have their own genome and ribosomes that carry out protein synthesis inside the mitochondria[1]
The two most well-known mitochondrial diseases associated with mt-tRNA mutations are MELAS and myoclonic epilepsy with ragged red fibers (MERRF)

Summary

Introduction

Mitochondria are double-membrane bound organelles found in most eukaryotic organisms with the important function of generating cellular energy via oxidative phosphorylation, but which function in cellular signaling, cellular differentiation, cell death, and cell cycle regulation. The first report of a mt-tRNA mutation causing human disease was published in 1990 when Kobayashi et al.[11] revealed that a mutation in the mitochondrial tRNALeu gene (MTTL1) was causative of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)[11,12]. Over 300 mutations in mt-tRNA genes have been identified to cause human disease [Table 1]. The two most well-known mitochondrial diseases associated with mt-tRNA mutations are MELAS and myoclonic epilepsy with ragged red fibers (MERRF).

Results

Conclusion