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Cell-penetrating peptide facilitated translocation is a topic of great debate. Evidence has been presented that translocation could use several different pathways for uptake. In addition, the mechanism of translocation can be dependent on whether the peptide is free or attached to cargo.
A target peptide is a short (3-70 amino acids long) peptide chain that directs the transport of a protein to a specific region in the cell, including the nucleus, mitochondria, endoplasmic reticulum (ER), chloroplast, apoplast, peroxisome and plasma membrane.
The targeting peptides of these proteins have a high content of basic and hydrophobic amino acids, a low content of negatively charged amino acids. They have a lower content of alanine and a higher content of leucine and phenylalanine. The dual targeted proteins have a more hydrophobic targeting peptide than both mitochondrial and chloroplastic ...
Mitochondrial proteins which reach the innermost mitochondrial compartment, the Mitochondrial matrix, often undergo proteolytic cleavage of the targeting signal, performed by the Mitochondrial Processing Peptidase (MPP), this is often necessary for the maturation of the preprotein to its functional form or to reveal additional targeting sequences.
[55] [56] Efficiencies of around 1% endosomal escape have been reported for most non-viral carrier strategies, including lipid nanoparticles and cell-penetrating peptides . [ 56 ] [ 52 ] [ 57 ] Moreover, the exact mechanisms of endosome escape remain unclear and are a matter of ongoing research .
A close up of a single ribosome in coordination with the TOM complex on the outer Mitochondrial membrane and the TIM complex on the inner Mitochondrial membrane (bottom image). The nascent transmembrane protein is being fed into the mitochondrial membrane where its target peptide (not shown) gets cleaved.
Mitochondrial intermediate peptidase is an enzyme that in humans is encoded by the MIPEP gene. [5] This protein is a critical component of human mitochondrial protein import machinery involved in the maturing process of nuclear coded mitochondrial proteins that with a mitochondrial translocation peptide, especially those OXPHOS-related proteins.
[8] [9] It is a potent protein disaggregase that chaperones the mitochondrial intermembrane space. [10] Mutations in the CLPB gene could cause autosomal recessive metabolic disorder with intellectual disability/developmental delay, congenital neutropenia , progressive brain atrophy, movement disorder, cataracts , and 3-methylglutaconic aciduria .