Lecture 2: mitochondria Flashcards
What is a mitochondrion?
> Membrane- enclosed organelle
Plural is mitochondria
Functions of mitochondria
Involved in:
> Cell signalling
> Cell differentiation
> Cell death
> Control of the cell cycle
and cell growth
Mitochondrial localisation
> In all aerobic eukaryotic cell
Clustered in regions of greatest metabolic activity
-Greatest need of ATP
How did mitochondria arise?
> Endosymbiotic theory
-mitochondria are
descended from ancient
bacteria, which were
engulfed by the ancestors
of eukaryotic cells more
than a billion years ago.
How do we know this?
-mitochondria contain
organelles themselves
->ribosomes
->own independent genome (similar to bacterial genome)
Structure of mitochondria
Composed of compartments that carry out specialised functions:
> ATP synthase particles
> Inner membrane
> Outer membrane
> DNA
> Granules
> Ribosome
> Cristae
> inner membrane space
> Matrix
Mitochondrial proteins
> Mitochondrial proteins vary depending on the tissue and species
-humans have 615 distinct
types of mitochondrial
proteins identified from
cardiac mitochondria
-mice have 940
mitochondrial proteins
encoded by different genes
–> they’re smaller
The mitochondrial protenome is thought to be dynamically regulated
Outer membrane
> Encloses the entire organelle
Has protein-to-phospholipid ratio similar to the plasma membrane (about 1:1 by weight)
Contains large numbers of integral proteins called poring
-channels that allow
molecules <5000 Da to
freely diffuse across the
membrane
Large proteins can enter if they have a signalling sequence to utilise an active transport protein called a translocase
Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol
-leads to cell death
Metabolic functions
-Phospholipid synthesis
-Fatty acid desaturation
-Fatty acid elongation
Intermembrane space (proteins)
> Space between the outer membrane and the inner membrane
Same concentrations of small molecules (ions and sugars) as cytosol
-As outer membrane is
freely permeable
Protein comparison differs to that of the cytosol
-As active transport
needed
One protein that is localised to the intermembrane space is cytochrome C
-part of the electron
transport chamber
ATP synthase
> An enzyme that synthesises ATP from ADP and inorganic phosphate (Pi)
ATP synthesis uses energy
- Protons (H+) moving
down an electrochemical
gradient from the inter-
membrane space into the
matrix
Inner membrane (phospholipids)
> Has a very high protein-to-phospholipid ratio
- More than 3:1 by weight
(~1 protein for 15
phospholipids)
Is rich in an unusual phospholipid called cardiolipin
- Cardiolipin contains four fatty acids rather than two and may help to make the inner membrane impermeable
Almost all ions and molecules require special membrane transporters to enter or exit the matrix
Metabolic functions
- Electron transport
- Oxidative
phosphorylation
- Pyruvate import
- Fatty acyl CoA import
- Metabolite transport
Cristae
> Invaginations of inner membrane
Expand the surface area of the inner mitochondrial membrane
- In typical liver
mitochondria, the
surface area (including
cristae) is about 5 x that
of the outer membrane
Enhance its ability to produce ATP
Muscle cell mitochondria contain more cristae than typical liver mitochondria as greater demand for ATP
Mitochondrial network or discrete organelle?
> Typically pictured as oval shaped discrete organelles
New theory
- Extensively branched
- Fewer
- Larger size
» Constantly in flux
»_space; Segments pinch off
and fuse with other
mitochondria
Matrix
> Space enclosed by the inner membrane
Contains:
- About 2/3 of the total
protein in a
mitochondrion
- Highly-concentrated
mixture of hundreds of
enzymes
- Special mitochondrial
ribosomes
- tRNA
- Several copies of the
mitochondrial DNA
genome
Important in the production of ATP with the aid of the ATP synthase contained in the inner membrane
Major functions of the enzymes include:
- Oxidation of pyruvate and
fatty acids
- Citric acid (Kreb’s) cycle
Metabolic functions
- Pyruvate oxidation
- TCA cycle
- beta oxidation of fats
- DNA replication
- RNA synthesis
(transcription)
- Protein synthesis
(translation)
Mitochondrial DNA
> Cell has 100s of mitochondria each with 2-10 copies of mtDNA
- Heterogeneous within
tissues
Codes for some but not all of its own proteins
16,568 bp
37 genes
- 13 protein-encoding
regions for respiratory
complexes
- 2 for rRNAs
- 22 for tRNAs
Needed for synthesis of the 13 mitochondrial proteins
Mitochondrial diseases
> Genetic defects of muscle or nerve tissue
- High consumers of ATP
Severe
- Infant death, blindness,
deafness, seizures, stroke-
like episodes
Milder
- Muscle weakness,
intolerance of exercise,
muscle deterioration,
infertility (non-motile
sperm)
May play a role in the ageing process
Most defects in genes encoding mitochondrial tRNA
- Particularly those for
leucine and isoleucine
- See translation lecture for
more on tRNA
Arise when most of mitochondria in a tissue have a certain mutant gene
Maternal inheritance from mitochondria from egg not sperm
