Outer mitochondrial membrane E3 Ub ligase MARCH5 controls mitochondrial steps in peroxisome biogenesis

Insights

Mitochondrial E3 Ub ligase MARCH5 is essential for creating new peroxisomes from mitochondria. Its absence halts peroxisome development, supporting a hybrid model of organelle biogenesis.

Area of Science:

  • Cell Biology
  • Organelle Biogenesis
  • Mitochondrial Dynamics

Background:

  • Peroxisome de novo biogenesis is a complex process requiring mitochondrial contributions.
  • The precise mitochondrial proteins involved in initiating peroxisome formation remain largely unidentified.
  • Understanding these mitochondrial factors is crucial for elucidating peroxisome biogenesis pathways.

Approach:

  • Investigated the role of the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 in peroxisome biogenesis.
  • Utilized MARCH5 knockout and activity-deficient mutants to assess its function.
  • Examined the impact of MARCH5 depletion on peroxisome formation, protein expression, and localization, including interactions with Pex14 and Tom20.

Key Points:

  • MARCH5 is vital for generating mitochondria-derived pre-peroxisomes, controlling their maturation.
  • MARCH5 knockout leads to immature peroxisomes and reduced expression of peroxisomal proteins.
  • MARCH5 acts upstream of Pex14 in the mitochondrial phase of peroxisome biogenesis.

Conclusions:

  • MARCH5 is an essential mitochondrial protein that initiates peroxisome biogenesis.
  • The findings validate the hybrid, mitochondria-dependent model of peroxisome biogenesis.
  • MARCH5's role highlights a critical link between mitochondrial function and peroxisome formation.

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,...
3.1K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.1K
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...
4.4K
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.0K
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...
2.6K
Protein Import into the Peroxisomes01:27

Protein Import into the Peroxisomes

Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
3.5K