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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

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.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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.
Most of the mitochondrial precursors...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...

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Related Experiment Video

Updated: Jul 6, 2026

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria
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The mitochondrial protease AFG3L2 is essential for axonal development.

Francesca Maltecca1, Asadollah Aghaie, David G Schroeder

  • 1Human Molecular Genetics Unit, and Neuropathology Unit and Istituto di Neurologia Sperimentale, San Raffaele Scientific Institute, 20132 Milan, Italy.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|March 14, 2008
PubMed
Summary

Mitochondrial metalloprotease AFG3L2 is crucial for axonal development. Its dysfunction causes severe impairment, unlike paraplegin mutations, highlighting AFG3L2

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Area of Science:

  • Mitochondrial biology
  • Neuroscience
  • Genetics

Background:

  • AFG3L2 and paraplegin form a mitochondrial supracomplex for protein quality control.
  • Mutations in paraplegin cause hereditary spastic paraplegia, affecting upper motoneurons.
  • The precise role of AFG3L2 in neuronal development and disease remains less understood.

Purpose of the Study:

  • To investigate the function of AFG3L2 in neuronal development using novel mouse models.
  • To compare the molecular and phenotypic consequences of AFG3L2 loss-of-function with paraplegin deficiency.
  • To elucidate the molecular mechanisms underlying AFG3L2's role in mitochondrial function and axonal integrity.

Main Methods:

  • Generation and characterization of Afg3l2 knockout and missense mutant mouse models.
  • Comparative analysis of axonal development, myelination, and survival in Afg3l2 and paraplegin mutant mice.
  • Molecular studies investigating AFG3L2 expression, oligomerization, and interaction with paraplegin.

Main Results:

  • Afg3l2 mutant mice exhibit severe axonal development defects, delayed myelination, and early lethality (P16).
  • These phenotypes are more severe than those observed in paraplegin-deficient mice.
  • AFG3L2 displays higher neuronal expression and supports both homo- and hetero-oligomerization, unlike paraplegin.

Conclusions:

  • AFG3L2 plays a critical role in linking mitochondrial metabolism to axonal development, with a more pronounced impact than paraplegin.
  • AFG3L2 is a key regulator of mitochondrial protein homeostasis essential for neuronal integrity.
  • AFG3L2 is a potential candidate gene for early-onset motoneuron and cerebellar diseases of unknown etiology.