scholarly journals Local protein synthesis of mtIF3 regulates mitochondrial translation for axonal development

2021 ◽  
Author(s):  
Soyeon Lee ◽  
Dongkeun Park ◽  
Chunghun Lim ◽  
Jae-Ick Kim ◽  
Kyung-Tai Min
Keyword(s):  
Axonal Growth ◽  
Growth Cones ◽  
Small Subunit ◽  
Bimolecular Fluorescence Complementation ◽  
Initiation Factor ◽  
Mitochondrial Translation ◽  
Local Protein Synthesis ◽  
Mitochondrial Ribosomes ◽  
Axonal Development ◽  
Local Protein

AbstractMitochondrial initiation factor 3 (mtIF3) binds to and dissociates mitochondrial ribosomes. The mtIF3-small subunit complex then recruits mtIF2, mRNA, and N-formylmethionine-tRNA to initiate mitochondrial translation. Intriguingly, transcripts of the nuclear-encoded mtIF3 gene have been shown present in axonal growth cones; however, the biological function of this compartmentalization remains largely unknown. Here, we demonstrate that brain-derived neurotrophic factor (BDNF) induces local translation of mtIF3 mRNA in axonal growth cones. Subsequently, mtIF3 protein is translocated into axonal mitochondria and promotes mitochondrial translation as assessed by our newly developed bimolecular fluorescence complementation sensor for the assembly of mitochondrial ribosomes. We further show that BDNF-induced axonal growth requires mtIF3-dependent mitochondrial translation in axons. These findings provide new insight into how neurons adaptively control mitochondrial physiology and axonal development via local mtIF3 translation.

scholarly journals mtIF3 is locally translated in axons and regulates mitochondrial translation for axonal growth

BMC Biology ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Soyeon Lee ◽  
Dongkeun Park ◽  
Chunghun Lim ◽  
Jae-Ick Kim ◽  
Kyung-Tai Min
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Bimolecular Fluorescence Complementation ◽  
Initiation Factor ◽  
Mitochondrial Translation ◽  
Functional Changes ◽  
Neural Connections ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Functions

Abstract Background The establishment and maintenance of functional neural connections relies on appropriate distribution and localization of mitochondria in neurites, as these organelles provide essential energy and metabolites. In particular, mitochondria are transported to axons and support local energy production to maintain energy-demanding neuronal processes including axon branching, growth, and regeneration. Additionally, local protein synthesis is required for structural and functional changes in axons, with nuclear-encoded mitochondrial mRNAs having been found localized in axons. However, it remains unclear whether these mRNAs are locally translated and whether the potential translated mitochondrial proteins are involved in the regulation of mitochondrial functions in axons. Here, we aim to further understand the purpose of such compartmentalization by focusing on the role of mitochondrial initiation factor 3 (mtIF3), whose nuclear-encoded transcripts have been shown to be present in axonal growth cones. Results We demonstrate that brain-derived neurotrophic factor (BDNF) induces local translation of mtIF3 mRNA in axonal growth cones. Subsequently, mtIF3 protein is translocated into axonal mitochondria and promotes mitochondrial translation as assessed by our newly developed bimolecular fluorescence complementation sensor for the assembly of mitochondrial ribosomes. We further show that BDNF-induced axonal growth requires mtIF3-dependent mitochondrial translation in distal axons. Conclusion We describe a previously unknown function of mitochondrial initiation factor 3 (mtIF3) in axonal protein synthesis and development. These findings provide insight into the way neurons adaptively control mitochondrial physiology and axonal development via local mtIF3 translation.

scholarly journals Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones

2015 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Michael Piper ◽  
Aih Lee ◽  
Francisca van Horck ◽  
Heather McNeilly ◽  
Trina Lu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Microtubule Cytoskeleton ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Erratum to: Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Michael Piper ◽  
Aih Cheun Lee ◽  
Francisca P.G van Horck ◽  
Heather McNeilly ◽  
Trina Bo Lu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Microtubule Cytoskeleton ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Local Protein Synthesis in Axonal Growth Cones

2007 ◽  
Vol 1 (4) ◽  
pp. 179-184 ◽  
Author(s):  
Saulius Satkauskas ◽  
Dominique Bagnard
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy

2019 ◽  
Vol 28 (16) ◽  
pp. 2711-2719 ◽  
Author(s):  
Enrico Bugiardini ◽  
Alice L Mitchell ◽  
Ilaria Dalla Rosa ◽  
Hue-Tran Horning-Do ◽  
Alan M Pitmann ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Mitochondrial Protein ◽  
In Silico Analysis ◽  
Small Subunit ◽  
Mitochondrial Translation ◽  
Transgenic Expression ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Ribosome ◽  
Protein Components ◽  
Biochemical Analyses

Abstract Mitochondrial disorders are clinically and genetically heterogeneous and are associated with a variety of disease mechanisms. Defects of mitochondrial protein synthesis account for the largest subgroup of disorders manifesting with impaired respiratory chain capacity; yet, only a few have been linked to dysfunction in the protein components of the mitochondrial ribosomes. Here, we report a subject presenting with dyskinetic cerebral palsy and partial agenesis of the corpus callosum, while histochemical and biochemical analyses of skeletal muscle revealed signs of mitochondrial myopathy. Using exome sequencing, we identified a homozygous variant c.215C>T in MRPS25, which encodes for a structural component of the 28S small subunit of the mitochondrial ribosome (mS25). The variant segregated with the disease and substitutes a highly conserved proline residue with leucine (p.P72L) that, based on the high-resolution structure of the 28S ribosome, is predicted to compromise inter-protein contacts and destabilize the small subunit. Concordant with the in silico analysis, patient’s fibroblasts showed decreased levels of MRPS25 and other components of the 28S subunit. Moreover, assembled 28S subunits were scarce in the fibroblasts with mutant mS25 leading to impaired mitochondrial translation and decreased levels of multiple respiratory chain subunits. Crucially, these abnormalities were rescued by transgenic expression of wild-type MRPS25 in the mutant fibroblasts. Collectively, our data demonstrate the pathogenicity of the p.P72L variant and identify MRPS25 mutations as a new cause of mitochondrial translation defect.

scholarly journals Regulation of retinal axon growth by secreted Vax1 homeodomain protein

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Namsuk Kim ◽  
Kwang Wook Min ◽  
Kyung Hwa Kang ◽  
Eun Jung Lee ◽  
Hyoung-Tai Kim ◽  
...  
Keyword(s):  
Axon Growth ◽  
Axonal Growth ◽  
Optic Chiasm ◽  
Homeodomain Protein ◽  
Retinal Ganglion ◽  
Factor Activity ◽  
Local Protein Synthesis ◽  
Hypothalamic Cells ◽  
Retinal Axon ◽  
Local Protein

Retinal ganglion cell (RGC) axons of binocular animals cross the midline at the optic chiasm (OC) to grow toward their synaptic targets in the contralateral brain. Ventral anterior homeobox 1 (Vax1) plays an essential role in the development of the OC by regulating RGC axon growth in a non-cell autonomous manner. In this study, we identify an unexpected function of Vax1 that is secreted from ventral hypothalamic cells and diffuses to RGC axons, where it promotes axonal growth independent of its transcription factor activity. We demonstrate that Vax1 binds to extracellular sugar groups of the heparan sulfate proteoglycans (HSPGs) located in RGC axons. Both Vax1 binding to HSPGs and subsequent penetration into the axoplasm, where Vax1 activates local protein synthesis, are required for RGC axonal growth. Together, our findings demonstrate that Vax1 possesses a novel RGC axon growth factor activity that is critical for the development of the mammalian binocular visual system.

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