Transport of protein in

mitochondrail membrane .
MADE BY PRATEEK GANGWANI.
ROLL NO
14/IBT/032
Topic to discuss
* translocation of protein across mitochondrail
membrane
* how transport molecule transport across
appropriate vesicle .
* Molecular mechanism of driving the mitchondrail
protein sorting inter and outer membrane
* human prespective with mechanism when
mutation occur in mitochondrail pathways .

INTRACELLULAR COMPARTMENTS AND TRANSPORT OF

PROTEIN IN MITOCHONDRAIL MEMBRANES .
Mitochondria
contains its own DNA
, ribosomes and other
components required
for protein synthesis,
.
most of their proteins
are encoded in the
cell nucleus and
imported from cytosol
. Each imported
protein must reach
the particular
organelle
subcompartment in
which it functions.

Mitochondrail genome .
* The growth of mitochondria depends
mainly on the import of proteins from the
cytosol. The imported proteins must be
transported across a number of
membranes in succession and end up in
the appropriate place. The process of
protein movement across membranes is
often called protein translocation.

Transport of protein across mitochondrail membrane .

Most mitochondrial proteins are encoded by nuclear genes and imported
from the cytosol. Proteins unfold to enter mitochondrial . The protein is
translocated simultaneously across both the inner and outer membranes
at specialized sites where the two membranes are in contact with each
other

Chaperone
proteins help
pull proteins
across and help
it refold

SRP (signal-recognition particle) binds the ER signal sequence on the

mRNA. This slows protein synthesis. Once SRP bind its receptor in the
ER membrane and docks with the translocation channel, it is released
and protein synthesis resumes.

Amino terminus

The signal sequence opens the translocation channel. The ribosome

remains attached while the rest of the protein is threaded through the
membrane. Signal peptidase cleaves the signal sequence.

Start and Stop signals determine the arrangement of a transmembrane

protein in the lipid bilayer.

The integration of a double pass transmembrane protein.

Complex multipass proteins

contain further pairs of stop
and start sequences.

..

Clathrin-coated vesicles bud from the golgi on the outward secretory

pathway and from the plasma membrane on the inward endocytic
pathway. Clathrin molecules assemble on the cytosolic surface of the
membrane - this starts the shaping of the membrane
into a vesicle. A small GTP-binding protein dynamin - forms a ring around the neck. GTP is
hydrolized, the ring constricts, pinching
off
the neck and
releasing the
vesicle.

1. How does the transport vesicle select the appropriate molecules to

transport? Excluding all other?

In the clathrin system, adaptins bind the coat and the vesicle membrane.
These help select the molecules for transport because the adaptins bind
the membrane via specific cargo receptors.
Molecules to be
transported carry
specific transport
signals that bind to
specific cargo
receptors.

GTP --> GDP

Mitochondrial Protein
Import inter and outer
membraneand Human
Health
and
Disease

Most mitochondrial proteins are nuclearencoded and synthesised as preproteins

on polysomes in the cytosol. They must
be targeted to and translocated into
mitochondria. Newly synthesised
preproteins interact with cytosolic factors
until their recognition by receptors on the
surface of mitochondria

Proteins are then transferred from the receptors to

the general import pore of the outer membrane,
the TOM complex. Once across the outer
membrane, proteins are sorted to one of the four
intra-mitochondrial locations. Outer membrane
proteins are inserted into the membrane either by
the TOM or the sorting and assembly machinery
(SAM) complex.
Matrix proteins are sorted via the TIM23 complex
and the presequence translocase-associated motor
(PAM), while some single-pass inner membrane
proteins are directly inserted into the membrane.

Once matrix proteins cross the inner membrane, they

are processed and folded via mitochondrial processing
peptidase (MPP) and matrix chaperonins,
Some single-pass inner membrane proteins are reexported via OXA after being imported into the matrix.
Polytopic inner membrane proteins are guided across
the intermembrane space by the small Tim proteins
(Tim9/10, Tim8/13) to the TIM22 complex where they
are inserted into the inner membrane.
The red stars denote import factors that either cause a
disease state, or represent acquired changes.

Flow chart how transport of protein in mitochondrail

inter membrane and out membrane

ATP Hydrolysis and a Membrane Potential

Drive Protein Import Into the Matrix Space

Acquired defects in
mitochondrial protein import
1 ConditionEffectRefsAgingReduction in
the import of mitochondrial proteins
needed for DNA repair .2 Chronic muscle
stimulationIncreased rate of import and
increase in protein import machineries .3
Oxidative stressInhibits the import of
precursor proteins and leads to their
degradation . 4 Thyroid hormone (T3)
treatmentIncreased rate of import and
increases in protein import machineries.