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Webb et al. J Transl Genet Genom 2020;4:71-80 Journal of Translational
DOI: 10.20517/jtgg.2020.11 Genetics and Genomics

Review Open Access

Mitochondrial translation defects and human
disease

Bryn D. Webb, George A. Diaz, Pankaj Prasun

Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Correspondence to: Dr. Bryn D. Webb, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai,
One Gustave L. Levy Place, Box 1498, New York, NY 10029, USA. E-mail: bryn.webb@mssm.edu

How to cite this article: Webb BD, Diaz GA, Prasun P. Mitochondrial translation defects and human disease. J Transl Genet
Genom 2020;4:71-80. http://dx.doi.org/10.20517/jtgg.2020.11

Received: 7 Feb 2020 First Decision: 24 Feb 2020 Revised: 24 Apr 2020 Accepted: 6 May 2020 Available online: 23 May 2020
Science Editor: Andrea L. Gropman Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

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 V (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.

Keywords: Mitochondria, translation defect, tRNA, aminoacyl-tRNA synthetase, rRNA, ribosomal protein, mitochondrial
disease, mtDNA

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 also 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
[1]
and ribosomes that carry out protein synthesis inside the mitochondria . The mitochondrial genome, which
is housed in the mitochondrial matrix, encodes 37 genes: 13 which encode protein subunits of respiratory

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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