Synthesis and targeting of mitochondrial proteins

SUBMITTED BYPRACHEE RAJPUT

DEPARTMENT OF ZOOLOGY AND APPLIED AQUACULTURE BARKATULLAH UNIVERSITY BHOPAL

SYNOPSISINTRODUCTIONMITOCHONDRIAL PROTIENS SYNTHESISTARGETING OF MITOCHONDRIAL

PROTIENSCONCLUSIONREFERENCES

INTRODUCTIONMitochondrial 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 the cytosol.

defination • The proteins that are involved in the various

important processes of mitochondria viz. oxidative phosphorylation, kreb’s cycle, electron transport chain , ATP synthesis etc. are called mitochondrial proteins.

Mitochondrial proteins

Synthesis

The mitochondrial proteins are formed on the free ribosomes present in the cytosol. These proteins are then targeted to the mitochondria, chloroplasts , peroxisomes and nucleus.

Targeting of mitochondrial proteins

• The precursor proteins synthesized in the cytosol are designed for the matrix of mitochondria usually contain specific N- terminal uptake targeting sequences that specifically binding to receptor proteins present on the organelle surface.

• The important features of N- terminal of mitochondrial proteins have specific sequences of 3-5 non consecutive residue of arg. or lys. And theronine and serine may be present , but aspartate and glutamate are not present.

Import from cytosol to the outer surface of mitochondria

• In the cytosol, the soluble precursors of mitochondrial proteins (including hydrophobic integral membrane proteins) bind to one or more chaperones. These proteins use the energy released by ATP hydrolysis to keep nascent and newly made proteins in an unfolded state. Two chaperones, cytosolic Hsc70 and mitochondrial-import stimulation factor (MSF), have been shown to prevent the misfolding or aggregation of mitochondrial precursor proteins so that they can be taken up by mitochondria. MSF is also able to disperse aggregates of proteins. Some precursor proteins, such as the inner-membrane ATP/ADP antiporter, bind to MSF and the resulting complex then binds to a set of receptors called Tom37 and Tom70 on the outer membrane; Tom37 and Tom70 then transfer the precursor to a second set of receptors (Tom20 and Tom22) with release of MSF (Figure steps 1a, 2, and 3a)

Import through outer membrane of mitochonria

• Most precursor proteins bind to cytosolic Hsc70, which delivers the protein directly to the Tom20 and Tom22 receptors (steps 1b and 3b). These receptors are linked to Tom40, the actual channel in the outer membrane. When purified and incorporated into liposomes, Tom40 forms a transmembrane channel with a pore wide enough — about 1.5 to 2.5 nm in diameter — to accommodate an unfolded polypeptide chain.

• A precursor protein destined for the mitochondrial matrix passes through the Tom40 channel in the outer membrane and another channel in the inner membrane (Figure steps 4 and 5). Translocation into the matrix occurs only at “contact sites” where the outer and inner membranes are in close proximity and requires a proton-motive force across the inner membrane.

import through inner membrane of mitochondria

• One sub complex is represented by at least five proteins (Tim33, Tim23, Tim17, Tim14, and Tim11), most or all of them firmly embedded within the inner membrane; this sub complex appears to form a protein-conducting channel across the inner membrane. The second sub complex is represented by the peripheral membrane protein Tim44 and the chaperones mhsp70 and mGrpE. mhsp70 binds simultaneously to Tim44 on the matrix side of the inner membrane and to mGrpE; this sub complex appears to function as an ATP-driven “import motor” that pulls the precursor chain across the Tim channel into the matrix space. Interaction between the Tim sub complexes seems to be dynamic as they readily dissociate from each other upon solubilisation of the inner membrane under non-denaturing conditions.

Processing of proteins in mitochondrial matrix• The proteins as enters in the matrix of mitochondria, the uptake

targeting sequences are cleaved by another protein called signal peptidase. Recent work on protein import into the matrix of isolated yeast mitochondria has shown that different proteins fold with the aid of different chaperones; some interact indeed with hsp60/cpn10, but many others (perhaps even the majority) can fold rapidly without the aid of hsp60/cpn10. For some, folding appears to be aided by a matrix-localized complex containing mhsp70, Mdj1 (a mitochondrial DnaJ homolog), and mGrpE. Still other imported proteins additionally require the assistance of Cpr3, a mitochondrial proline isomerase. Since different proteins differ widely in their structure and folding pathways, it is perhaps not surprising that their folding in vivo is mediated by different chaperones.

Conclusion• Thus it is concluded that the synthesis of

mitochondrial proteins is well co-ordinated i.e. a close co-ordination of nuclear and mitochondrial genome expression.

references• Molecular Cell Biology Fifth Edition Harvey

Lodish et al.• World of cell by Becker• Internet sources.