(Powerhouse of the Cell)

MITOCHONDRIA

Saurav Saha 2014-11-106

Mitochondria (singular, mitochondrion) – are typically tubular or rod-shaped

organelles found in the cytoplasm of most cells and produces enzymes for the metabolic conversion of food to

energy.

 

FUNCTION

Energy conversion

The most prominent roles of mitochondria are to produce the energy currency of the cell, ATP, through respiration, and to regulate cellular metabolism.

A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task.

History

Mitochondria was first observed by kollikar in 1850

The present name was given by Benda in 1997

In 1882 flaming named the mitocondria flia

In 1912Kingsburry was suggested that oxidation raection are carried in mitocondria

Wotto warberg is father of respiratory he isolated large mitocondria molecule and found the enzyme associated withOxidaton process

STRUCTUREA mitochondrion contains outer and inner

membranes composed of phospholipid bilayers and proteins. The two membranes have different properties. Because of this double-membrane organization, there are five distinct parts to a mitochondrion. They are:

- encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane

Outer Membrane

contains large numbers of integral

proteins called porins. allow molecules to freely

diffuse from one side of the membrane to the other.

Outer membrane

Intermembrane Space

- is the space between the outer membrane and the inner membrane

It is also known as Perimitochondrial space.

Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol.

Intermembrane space

Inner Membrane - also double phospholipid layer

- it is the site of the production of ATP

FUNCTIONS:

those perform the redox reactions of oxidative

phosphorylation

ATP-synthase

Specific transport proteins

Protein import machinery

Mitochondria fission and fusion protein

Inner membrane

CRISTAE

- The folding of the inner membrane that allows more surface area,

enhancing its ability to produce ATP.

MATRIX - Fluid material that fills the area inside the inner membrane

The matrix is the space enclosed by the inner

membrane.

It contains about 2/3 of the total protein in a mitochondrion.

The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane.

Matrix

Chemical composition:

The outer membrane consists of 40% lipids and 60 percent proteins.  

The inner membrane is made up of 20% lipids and 80% proteins.  The electron transport enzymes, proton secreting proteins are virtually buried in the core of the inner membranes. 

Mitochondrial matrix also consists of a wide variety of enzymes. There are more than 120 kinds of enzymes of mitochondrial.

Mitochondrial matrix also contains DNA, RNA molecules.

Proteins encoded by mitochondrial - synthesized

on ribosomes within the organelles and directed to sub-compartment immediately

Most proteins within mitochondria – coded by nuclear DNA, imported through ER

Sorting of Proteins to Mitochondria

Localize proteins to mitochondria

20–50 amino acids in long, located at the N-terminus

Rich in hydrophobic amino acids, +ve charged basic amino acids (arginine and lysine), and hydroxylated amino acids (serine and threonine)

Generally lack -ve charged acidic residues (aspartate and glutamate)

Amphipathic - Assume an α-helical conformation with +ve amino acids on one side of the helix and hydrophobic amino acids on the other side

Mt have ~1000 general import pores

Only unfolded proteins can be imported into the mitochondrion

Chaperone proteins (Hsc70) keep nascent and newly made proteins in anunfolded state

Mitochondrial matrix-targeting sequences

Tom proteins for translocon of the outer membrane

Tom20, Tom22 – recognize N-terminal matrix targeting sequences

Tom40 – constitutes outer general import pore (unidirectional passive channel)

Tim23, Tim17 – Compose the inner membrane channel (Tim - translocon of the inner membrane)

Outer-membrane peptide import receptor proteins on mt

Precursor proteins are kept unfolded by

chaperones (Eg. Hsc70) Hsc70 - interacting with Tim44 and

localized to the translocation channels in the inner mitochondrial membrane

Precursor protein binds to an import receptor - near asite of contact with the inner membrane

Precursor will be transferred into the general import pore

Protein import into the mitochondrial matrix

(i) ATP hydrolysis by Hsc70 chaperone proteins This energy is spent to maintain bound precursor proteins in an

unfolded state

(ii) Matrix Hsc70 + Tim44 protein - molecular motor to pull the protein into the matrix

(iii) H+ electrochemical gradient (Protonmotive force) across the inner membrane

Transmembrane potential - 200 mV (4,00,000 V/cm electric gradient) Positive charges in the amphipathic matrix-targeting sequence is

electrophoresed into the matrix space by the inside-negative membrane potential

Three energy inputs for the import of proteins to Mt

Targeting of inner Mt-membrane proteins

Path B

Precursors contain both matrix-targeting sequence and internal multiple hydrophobic domains recognized by inner-membrane protein termed Oxa1

Translocate a portion of the precursor into matrix through Tom20/22 and Tim23/17 channels

Matrix-targeting sequence gets cleaved, protein inserted into the inner membrane (by interaction of Oxa1 and other inner-membrane proteins)

Path C For multi-pass proteins with 6 helices Precursor lacks N-terminal matrix-

targeting sequence but has multiple internal mitochondrial targeting sequences

Internal sequences on precursor are recognized by Tom70 (a second import receptor in the outer membrane)

Protein passes through Tom40 Second translocation complex in the

inner membrane is composed of Tim22/54

Tim9 and Tim10 (small proteins in inter-membrane spaces) transfer precursor to Tim22/54

Tim22/54 incorporate the multiple hydrophobic segments to the inner membrane

(ii) Targeting of Mt inter-membrane space proteins

Path A Precursor carries two different N-

terminal targeting sequences (both will be cleaved)

Targeting sequence closer to n-terminal is removed by Protease

The second targeting sequence (a hydrophobic segment) blocks complete translocation of the protein across the inner membrane

Protein gets inner-membrane embedded and diffuses laterally

A protease in the membrane cleaves the protein near the hydrophobic transmembrane segment

Mature protein is released into the intermembrane space

Path B No inner-membrane translocation factor is

involved Precursor is delivered directly to the

intermembrane space through general import pore

(iii) Targeting of Mt outer-membrane proteins A short matrix-targeting sequence at the N-

terminus is followed by a long stretch of hydrophobic amino acids

Hydrophobic sequence - stop-transfer sequence - prevents transfer of the protein into the matrix and anchors it in outer membrane

Neither the matrix-targeting nor stop-transfer sequence is cleaved from the anchored protein

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