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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Alternative Start Codon Connects eIF5A to Mitochondria.

Karina Danielle Pereira1,2, Letícia Tamborlin1, Letícia Meneguello1,2

  • 1Laboratory of Biotechnology, School of Applied Sciences, University of Campinas, Limeira, São Paulo, Brazil.

Journal of Cellular Physiology
|July 15, 2016
PubMed
Summary
This summary is machine-generated.

We identified a new form of eukaryotic translation initiation factor 5A (eIF5A) called isoform A. This isoform, unlike the common isoform B, targets mitochondria, suggesting a role in mitochondrial function.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Protein Biochemistry

Background:

  • Eukaryotic translation initiation factor 5A (eIF5A) is crucial for cellular processes.
  • eIF5A activity depends on the hypusine residue.
  • Human EIF5A1 transcript variants encode different eIF5A isoforms.

Purpose of the Study:

  • To validate the existence and production of eIF5A1 isoform A.
  • To investigate the functional differences between eIF5A1 isoforms A and B.
  • To determine the cellular localization and potential function of eIF5A1 isoform A.

Main Methods:

  • Mutagenic assays to analyze start codon efficiency.
  • Immunoblotting and mass spectrometry for protein characterization.
  • Mitochondrial co-purification assays to assess localization.

Main Results:

  • EIF5A1 transcript variant A produces both eIF5A1 isoforms A and B.
  • Isoform B is produced at higher levels than isoform A due to start codon efficiencies.
  • Both isoforms undergo hypusination and acetylation.
  • Isoform A, but not B, targets mitochondria.

Conclusions:

  • eIF5A1 isoform A exists and is produced from transcript variant A.
  • eIF5A1 isoform A possesses a mitochondrial targeting signal in its N-terminal extension.
  • eIF5A1 isoform A likely plays a role in mitochondrial function.