Lecture series D6
“Mitochondria and the cytoskeleton”
notes based on Alberts et al 4th ed. (2002) Chapters 14 and
16
prepared by T. J. Newman, November 13-November 15, 2005
revised by T. J. Newman, October 29, 2006
this document not
for public use – all images copyright Garland Science Publishing 2002
INTRODUCTION TO
MITOCHONDRIA
·
In eukaryotes,
specialized energy converting organelles exist within the cytosol
o
these are mitochondria (and plastids
[e.g. chloroplasts] in plants)
o
mitochondria
contain large amounts of tightly folded internal membrane
o
ATP is produced
through a process known as “chemiosmotic coupling”
§
high-energy
electrons are transferred along a series of membrane-bound electron carriers
§
these electrons
release energy that is used to pump protons across the membrane
§
this creates an electrochemical gradient
§
protons flow back
through the membrane via the protein ATP synthase
§
this catalyzes
the production of ATP
·
In contrast to mitochondria,
for which carbohydrates and O2 are inputs to ATP production,
o
in chloroplasts, these are the outputs from a process
driven by energy from sunlight
·
It is strongly
believed that mitochondria and chloroplasts derived from symbiotic prokaryotic
systems
o
a large element
of the evidence for this belief is that these organelles contain their own DNA
o
this DNA codes
for some of the proteins used in these organelles
o
however, many
other necessary proteins are coded in the nuclear DNA, synthesized in the
cytosol, and imported in the organelles
STRUCTURE
AND FUNCTION OF THE MITOCHONDRIAN
·
animal cells rely
on mitochondria for aerobic respiration (production of ATP via oxidative
metabolism)
·
glycolysis breaks down glucose to
pyruvate and creates 2 ATP
molecules
·
oxidative metabolism takes this
pyruvate and produces roughly 30 more ATP molecules
·
mitochondria are
not static organelles:
o
they constantly
change shape and occasionally fuse with one another
o
they are often
associated with microtubules
§
e.g. in figure
below, chains of mitochondria are arranged along a network of microtubules
o
they sometimes
reside in particular regions of the cell in which large amounts of ATP are
required
§
e.g. packed
around the flagellum of a sperm cell
·
A mitochondrian
has the following structure:
o
it is encompassed
by the outer membrane
o
this encloses the
inner membrane,
the space between is termed the intermembrane space
§
the inner
membrane contains a phospholipids called cardiolipin which has four fatty acid
tails and helps to make the inner membrane highly impermeable
o
the inner membrane
encloses the matrix
o
the inner
membrane contains the membrane proteins responsible for oxidative phosphorylation
·
Recall from our
lectures on metabolism, the citric acid cycle takes pyruvate and converts it to
acetyl CoA, which is then used to produce NADH and other high energy electron
carriers
·
Oxidative
phosphorylation is the process by which these high
energy electrons are
gradually “de-energized” finally being combined with molecular
oxygen to produce water,
and in the process creating a proton gradient, which is then used to drive phosphorylation of ADP
to ATP
·
ADP from the
cytosol is rapidly shuttled into the mitochondria for “recharging” to ATP
o
for a given ATP
molecule, this process repeats as often as one per minute
·
These processes involve
several large protein complexes
·
The electron
transfer process involves three large
multisubunit protein complexes:
o
NADH dehydrogenase complex
§
accepts electrons
from NADH
§
passes then
through at least seven iron-sulphur centers
§
then passes them
to ubiquinone
o
cytochrome
b-c1 complex
§
takes electron
from ubiquinone and passes them to
cytochrome c
o
cytochrome oxidase complex
§
accepts electron
from cytochrome c and passes them, 4 at a time, to oxygen
o
these reactions
are complex and are designed to control the highly energetic process of
breaking molecular oxygen into oxygen ions and then converting them to water
§
oxygen is
“controlled” by being clamped between a heme-linked iron atom and a copper atom
in cytochrome oxidase, as illustrated below
·
this is crucial,
since O2 with a single electron is a highly reactive radical
§
this reaction
accounts for 90% of molecular oxygen uptake in cells
§
poisons such as
cyanide and azide are so toxic since they halt electron transport by binding to
the cytochrome oxidase complexes
o
the structure of
cytochrome oxidase was recently determined from X-ray crystallography:
·
ATP synthase is a
multisubunit protein complex with a mass of 500K Daltons
o
it contains a
structure which is caused to rotate by the energy released from protons moving
down the electrochemical gradient
o
ADP and phosphate
groups are bound in the head region of the protein complex
o
these are
converted to ATP by conversion of the mechanical energy to chemical energy
o
the ATP synthase
can produce 100 molecules of ATP per second
o
each ATP requires
3-4 protons to pass through the protein complex
THE GENETIC SYSTEM OF
MITOCHONDRIA