Mitochondrial protein synthesis: Figuring the fundamentals, complexities and complications, of mammalian mitochondrial translation

Mitochondrial protein synthesis is essential for all mammals, being responsible for providing key components of the oxidative phosphorylation complexes. Although only thirteen different polypeptides are made, the molecular details of this deceptively simple process remain incomplete. Central to this process is a non‐canonical ribosome, the mitoribosome, which has evolved to address its unique mandate. In this review, we integrate the current understanding of the molecular aspects of mitochondrial translation with recent advances in structural biology. We identify numerous key questions that we will need to answer if we are to increase our knowledge of the molecular mechanisms underlying mitochondrial protein synthesis.

• Publication year

  2014

• Venue

  FEBS Letters

• Publication date

  2014-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.febslet.2014.05.054PMID 24911204PMCID 4099522
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Initial steps in RNA processing and ribosome assembly occur at mitochondrial DNA nucleoids.

  2014cited by this paper
• Cryo-EM structure of the small subunit of the mammalian mitochondrial ribosome

  2014cited by this paper
• The Structure of the Yeast Mitochondrial Large Ribosomal Subunit

  2014influential reference
• Mitoribosomal regulation of OXPHOS biogenesis in plants

  2014cited by this paper
• Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature.

  2014cited by this paper
• Delineation of C12orf65-related phenotypes: a genotype–phenotype relationship

  2014cited by this paper
• Phenotypic investigations of the depletion of EngA in Escherichia coli are consistent with a role in ribosome biogenesis.

  2014cited by this paper
• Correlative light- and electron microscopy with chemical tags.

  2014cited by this paper
• Mutations in the mitochondrial gene C12ORF65 lead to syndromic autosomal recessive intellectual disability and show genotype phenotype correlation.

  2013cited by this paper
• GRSF1 Regulates RNA Processing in Mitochondrial RNA Granules

  2013cited by this paper
• Structural basis for S-adenosylmethionine binding and methyltransferase activity by mitochondrial transcription factor B1

  2013cited by this paper
• MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals

  2013cited by this paper
• Human G-proteins, ObgH1 and Mtg1, associate with the large mitochondrial ribosome subunit and are involved in translation and assembly of respiratory complexes

  2013cited by this paper
• Architecture of the large subunit of the mammalian mitochondrial ribosome

  2013influential reference
• Silencing of the Nuclear RPS10 Gene Encoding Mitochondrial Ribosomal Protein Alters Translation in Arabidopsis Mitochondria[W]

  2013cited by this paper
• Specialization from synthesis: How ribosome diversity can customize protein function

  2013cited by this paper
• Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid*

  2013cited by this paper
• Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy

  2013cited by this paper
• The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression.

  2013cited by this paper
• Transcription-independent role for human mitochondrial RNA polymerase in mitochondrial ribosome biogenesis

  2013cited by this paper
• Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit

  2012cited by this paper
• Regulation of mammalian mitochondrial translation by post-translational modifications.

  2012cited by this paper
• Mitochondrial DNA nucleoid structure.

  2012cited by this paper
• Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis

  2012cited by this paper
• Mutation in PNPT1, which encodes a polyribonucleotide nucleotidyltransferase, impairs RNA import into mitochondria and causes respiratory-chain deficiency.

  2012cited by this paper
• The post-transcriptional life of mammalian mitochondrial RNA.

  2012cited by this paper
• Solution structure and siRNA‐mediated knockdown analysis of the mitochondrial disease‐related protein C12orf65

  2012cited by this paper
• A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55)

  2012cited by this paper
• C7orf30 is necessary for biogenesis of the large subunit of the mitochondrial ribosome

  2012cited by this paper
• Mitochondrial transfection for studying organellar DNA repair, genome maintenance and aging.

  2011cited by this paper
• A starter kit for point-localization super-resolution imaging.

  2011cited by this paper
• Assembly of bacterial ribosomes.

  2011cited by this paper
• Mitochondrial transformation: time for concerted action

  2011cited by this paper
• Biological significance of 5S rRNA import into human mitochondria: role of ribosomal protein MRP-L18.

  2011influential reference
• Contacts between mammalian mitochondrial translational initiation factor 3 and ribosomal proteins in the small subunit.

  2011cited by this paper
• A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms

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• Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

  2011cited by this paper
• Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation.

  2011cited by this paper
• Eukaryotic 5S rRNA biogenesis

  2011cited by this paper
• Mitochondrial tRNA import and its consequences for mitochondrial translation.

  2011cited by this paper
• Termination of Protein Synthesis in Mammalian Mitochondria*

  2011cited by this paper
• [EF-G2mt is an exclusive recycling factor in mammalian mitochondrial protein synthesis].

  2010cited by this paper
• Approaches toward super-resolution fluorescence imaging of mitochondrial proteins using PALM.

  2010cited by this paper
• Mitochondrial Enzyme Rhodanese Is Essential for 5 S Ribosomal RNA Import into Human Mitochondria*

  2010influential reference
• A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome

  2010cited by this paper
• Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit

  2010cited by this paper
• PNPASE regulates RNA import into mitochondria.

  2010cited by this paper
• Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect.

  2010cited by this paper
• Current Views of the Structure of the Mammalian Mitochondrial Ribosome

  2010influential reference
• Preferential Selection of the 5′-Terminal Start Codon on Leaderless mRNAs by Mammalian Mitochondrial Ribosomes

  2010cited by this paper
• Hungry Codons Promote Frameshifting in Human Mitochondrial Ribosomes

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• Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the Warburg Effect

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• Evidence for an active role of IF3mt in the initiation of translation in mammalian mitochondria.

  2009cited by this paper
• EF-G2mt is an exclusive recycling factor in mammalian mitochondrial protein synthesis.

  2009cited by this paper
• Import of tRNAs and aminoacyl-tRNA synthetases into mitochondria

  2009cited by this paper
• Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome.

  2009cited by this paper
• NAD+-dependent Deacetylase SIRT3 Regulates Mitochondrial Protein Synthesis by Deacetylation of the Ribosomal Protein MRPL10*

  2009cited by this paper
• HMRF1L is a human mitochondrial translation release factor involved in the decoding of the termination codons UAA and UAG

  2008cited by this paper
• Ribosomes bind leaderless mRNA in Escherichia coli through recognition of their 5'-terminal AUG.

  2008cited by this paper
• The human mitochondrial ribosome recycling factor is essential for cell viability

  2008cited by this paper
• Lack of secondary structure characterizes the 5' ends of mammalian mitochondrial mRNAs.

  2008cited by this paper
• A single mammalian mitochondrial translation initiation factor functionally replaces two bacterial factors.

  2008cited by this paper
• The Layered Structure of Human Mitochondrial DNA Nucleoids*

  2008cited by this paper
• Overexpression and purification of mammalian mitochondrial translational initiation factor 2 and initiation factor 3.

  2007cited by this paper
• Intragenomic 16S rDNA Divergence in Haloarcula marismortui Is an Adaptation to Different Temperatures

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• mtRF1a Is a Human Mitochondrial Translation Release Factor Decoding the Major Termination Codons UAA and UAG

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• A structural model for the large subunit of the mammalian mitochondrial ribosome.

  2006cited by this paper
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  2006cited by this paper
• Evolution of proteins in mammalian cytoplasmic and mitochondrial ribosomes

  2005cited by this paper
• In-vitro translation of mitochondrial mRNAs by yeast mitochondrial ribosomes is hampered by the lack of start-codon recognition

  2004cited by this paper
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  2004cited by this paper
• Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs.

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• Structure of the mammalian mitochondrial ribosome reveals an expanded functional role for its component proteins.

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• The ribosome filter hypothesis

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• Evolution of a protein-rich mitochondrial ribosome: implications for human genetic disease.

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• Modeling a minimal ribosome based on comparative sequence analysis.

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  2001cited by this paper
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  2000cited by this paper
• The structural basis of ribosome activity in peptide bond synthesis.

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  2000cited by this paper
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  1999cited by this paper
• Mammalian mitochondrial ribosomal proteins. N-terminal amino acid sequencing, characterization, and identification of corresponding gene sequences.

  1998cited by this paper
• Evidence for the presence of 5S rRNA in mammalian mitochondria.

  1998influential reference
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