Protein Import & Mitochondrial Assembly

How to protein Import

1. Protein Import And Mitochondrial Assembly . . Alankar

2. Contents Structure of Mitochondria Discription Some of mitochondrial proteins Diagram of mitochondria function About protein import Component of protein import and mitochondrial assembly. Protein Import across the outer membrane. Protein import across the inner membrane. Reference

3. Mitochondria : Structure

4. Mitochondrial proteins are essential for all mammals being responsible for providing key components for oxidative phosphorylation complexes, kreb’s cycle and electron transport chain. The mitochondrial proteins are very essential for the above processes so as to carry out the important functions of mitochondria i.e. ATP synthesis, the main function of mitochondria. The Process of ATP synthesis involve the assistance of various proteins. Some proteins are formed by the mitochondria itself and most of them are formed in cytosol .

5. Mitochondria: Function

6. About Protein Import Most m itochondrial genomes do not encode the protein required for DNA replication, transcription and translation. The nucleus contains gene that encode most of the mitochondrial proteins required for oxidative phosphorylation and all of the enzymes involved in mitochondrial metabolism. About 99% of mitochondrial proteins are synthesized on free cytosolic ribosomes and imported into mitochondria as completed polypeptide chain. Because of the double membrane structure of mitochondria, the import of proteins is complicated.

7. About Presequences Most proteins are targeted to mitochondria by amino-terminal sequences of 20-35 amino acid called presequences. These presequences are removed by proteolytic cleavage after their import into organelle. The presequences of mitochondrial proteins were first characterized by Gottfried Schatz. It contains multiple positively charged amino acid residues, usually in an ampiphatic alpha helix.

8. The main components of protein import and mitochondrial assembly Tom complex Tim complexes( Tim 22 and Tim 23 ) MPP( Matrix processing Peptidase ) Hsp70 chaperone

9. Protein import across the outer membrane The first step is the binding of presequences to receptors the on the surface of mitochondria. These receptors are the part of protein complex that directs translocation across the outer membrane ( Tom complex ). Tom complex consists of 7 different subunits. Tom20, Tom22 and Tom70 recognises precursor proteins and transfers them to central component. Tom 40 forms the channel. Three small Tom proteins Tom5, Tom6 and Tom7 are involved in the assembly and dynamics of Tom complex. Proteins are transferred to Tom40 pore protein and translocated across the outer membrane.

10. Protein import across the inner membrane The proteins are then transferred to a second protein complex in the inner membrane(Tim23). There are two Tim complexes – Tim22 and Tim23 complex. The Tim23 complex is formed by the three essential inner membrane proteins: Tim50 (with a receptor function in intermembrane space), Tim23 (channel-forming protein) and Tim17 (involved in motor recruitment). The Tim22 contains inner membrane proteins Tim18, Tim22 and Tim54.

11. Mitochondrial matrix proteins are then translocated across the inner membrane through Tim23. Some protein, which contain a second hydrophobic transmembrane targeting sequence, exit the Tim23 channel laterally and insert into the inner membrane. Translocation of proteins containing presequences through Tim23 requires the electrochemical potential established across the inner mitochondrial membrane during electron transport. The transfer of high energy electrons from NADH and FADH2 to molecular oxygen is coupled to the transfer of protons from the mitochondrial matrix to the intermembrane space. Since protons are charged particles, this transfer establishes an electric potential across the inner membrane, with the matrix being negative. During protein import, this electric potential drives translocation of the positively charged presequences .

12. complexes Proteins must be at least partially unfolded for translocation across the mitochondrial membrane. On the cytosolic side, members of the Hsp70 family of chaperone both maintains proteins in a partially unfolded state and present to the Tom complex. As they cross the inner membrane, the unfolded polypeptide chains are bound by another Hsp70 chaperone, which is the part of a motor complex that drives protein import.

13. References The cell : A molecular Approach sixth Edition M. Cooper et al. Life sceinces Fundamentals and Practices : Pranav Kumar and Usha Mina Molecular Cell Biology Fifth Edition Harvey Lodish et al.