Bioenergentics & Metabolism

Bioenergentics & Metabolism

Mitochondria

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Mitochondria Structure & Function

Generation of metabolic energy is a major activity of all

cells

Two cytoplasmic organelles are specifically devoted to

energy metabolism and production of ATP

• Mitochondria

Generates useful energy derived from breakdown of lipids

& carbohydrates

• Chloroplast

Use energy captured from sunlight to generate ATP and the

reducing power needed to synthesize carbohydrates from

CO2 and H2O

Mitochondria Structure & Function

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Mitochondria

Mitochondria are

◦ Responsible for most of the useful energy derived

from breakdown of carbohydrates and fattyacids

Converted to ATP by oxidative phosphorylation

Mitochondria are unique among cytosolic organelles in

that

They contain their own DNA which encodes

tRNA, rRNA, and some other mitochondrial proteins

Assembly of mitochondria contain

• Proteins encoded by their own genome

• Proteins encoded by nuclear genome and imported from cytosol

Mitochondria Structure & Function

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Structure of Mitochondria

Mitochondria are surrounded by a double

membrane system

• Consist of inner and outer membrane

separated by intermembrane space

• Innermembrane form numerous folds

(cristae) which extends into matrix • Large surface area

• Matrix contains mitochondrial genetic system & enzymes responsible for

oxidative metabolism

• Houses the machinery for aerobic respiration

Mitochondria Structure & Function

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Mitochondria consist of two aqueous compartments

Interior – the matrix

Between the inner and outer membranes – intermembrane space

Inner Membrane

High percentage of proteins(> 70%)

Involved in oxidative phosphorylation

• Transport of metabolites (pyruvate, fatty acids)

Impermeable to most ions and small molecules

a property critical to determining proton gradient that drives oxidative phosphorylation

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Mitochondria Structure & Function

Outer Membrane

Porins – integral proteins

Large internal channel

Allows free diffusion of molecules smaller than

about 1000 daltons

Composition of intermembrane is therefore similar to

cytosol with respect to ions and small molecules

Mitochondria Structure & Function

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Mitochondria are positioned near to locations

of high energy use i-e synapses in nerve cells,

muscle cells

Continuously fusing and dividing , remodel the

network of mitochondria in cell, and affect

function and morphology

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Mitochondria Structure & Function

Endosymbiotic Origin

Mitochondria contain their own genetic system

Mitochondria are thought to have evolved from bacteria

that developed a symbiotic relationship in which they

lived within larger cells (Endosymbiosis)

Genomes of living organisms that are similar to

mitochondria are that of

α-proteobacterium Rickettsia prowazeki

It is able to reproduce only in eukaryotic cells

But unlike mitochondria it transcribes most of its

own genes

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Mitochondria Structure & Function

Mitochondrial Genome

Mitochondrial genome are usually circular DNA

molecules, like bacteria

Present in multiple copies per organelle

Vary considerably in size between different species

Genomes of human and most other animal mitochondria

are only about 16kb

Larger mitochondrial genome are found in yeast (approx

80kb) and plants (more than 200kb)

e.g

Mitochondrial DNA in Arabidopsis is 367 kb, encodes only 31

proteins

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Mitochondria Structure & Function

Contd…

Smallest mitochondrial genome

◦ Protist: plasmodium falciparum 6kb, codes for only 3 proteins

Largest mitochondrial genome

◦ Protozoan Reclinomonas americana

◦ 69 kb and contain 67 genes

Most present day mitochondrial genome encode

◦ Small number of proteins

Mammalian mitochondria (1000 to 5000 different proteins)

representing approx 5% of proteins encoded by mammalian

genome

◦ tRNA, rRNA

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Mitochondria Structure & Function

Human mitochondrial 16 Kb

genome encodes

◦ Circular DNA molecule

◦ Maternal inheritance

Map

Origin of replication and transcriptional promoter sequences (D loop)

16sRNA, 12sRNA, 22tRNA

13 proteins (essential for oxidative phosphorylation)

Electron transfer chain complexes, including I, III, IV and V

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The Human Mitochondrial Genome

Mitochondrial Genetics

Mitochondria use a slightly different genetic code than

in prokaryotic and eukaryotic cells

Human mitochondria encode only 22 tRNAs ,approx

30 different tRNAs are required to translate the

universal code according to wobble rule

Translational of mitochondrial mRNA is accomplished by

extreme form of wobble

U in anticodon of tRNA can pair with any of four bases in

third codon position of mRNA

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Mitochondria Structure & Function

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Differences between the universal and Mitochondrial Genetic codes

Codon Universal Code Human Mitochondrial code

UGA Stop Trp

AGA Arg Stop

AGG Arg Stop

AUA IIe Met

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Mutations in mtDNA

Mitochondrial DNA can be altered by mutations

Germ-line mutations in mitochondrial DNA are transmitted from mother

• Mutation in tRNA gene

Metabolic syndrome; obesity, diabetes

• Mutation in gene that encode components of electron transport chain

Leber’s hereditary optic neuropathy; blindness

• Progressive Mutations in mitochondrial DNA

Aging

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Mitochondrial proteins

Contain 1000 to 5000 different proteins but nearly half of them remain unidentified (~5% of mammalian encoded proteins)

Mitochondria from different tissues contains different proteins (tissue specific functions)

Genes for mitochondrial proteins are in nucleus(95% of mt proteins)

Some of these genes were transferred to mitochondria by original prokaryotic ancestor

Cytosoloic protein synthesis mt transport

All kerb cycle enzymes/ rep/trans/translation

Complex because of mt double membrane

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Transport & assembly of matrix proteins

Pre-sequence, N-terminal 20-35 a.a target proteins to matrix

Partially unfolded by Hsp70 chaperon ◦ Prevent aggregation as emerge

from free ribosomes

Bind to receptors on Tom protein complex(translocase of outer membrane)

Bind Tim complex(Translocase of inner membrane)

The presequence is cleaved by a matrix protease

a mitochondrial Hsp70 binds the polypeptide chain as it crosses the inner membrane, driving further protein translocation.

A mitochondrial Hsp60 then facilitates folding of the imported polypeptide within the matrix

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