Mitochondrial Trafficking

Most mitochondrial proteins are synthesized on cytoplasmic ribosomes as precursor proteins that are then translocated into mitochondria via a highly specialized import system (8). Two broad classes of mitochondrial proteins exist: the majority contain a cleavable N-terminal "presequence" of between 20 and 60 amino acid residues. This group interacts with a multimeric complex on the outer mitochondrial membrane, known as the translocase of the outer membrane (Tom complex), specifically Tom20. After passing through the outer membrane, they enter the matrix by passing through a pore formed by a complex known as translocase of the inner membrane (Tim complex), specifically Tim23. After entry into the matrix, the presequence is cleaved off by the mitochondrial processing peptidase (MPP), and the mature protein is usually localized to the matrix (8). The second group of mitochondrial proteins does not contain a cleavable presequence but instead has internal signal sequences often consisting of stretches of positively charged amino acids adjacent to hydro-phobic domains. These proteins generally interact with the Tom70 receptor on the outer membrane, and, after entry, are localized to the inner mitochondrial membrane by interaction with the Tim22 complex (8). It is currently unclear at which residue the PINK1 leader sequence is cleaved, mitochondrial peptidase consensus sequences are difficult to predict and multiple sites may exist. Western blot analysis suggests that cleaved PINK1 is approximately 10 kDa shorter than the full-length protein; approximately 100 amino acids may therefore be cleaved from the preprotein (5). Currently, none of the known mutations are predicted to affect PINK1 trafficking or processing; however, some missense mutations have been reported outside the kinase domain at the N-terminus of the protein that could affect processing or folding.

Was this article helpful?

0 0
Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook

Post a comment